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1.
Article in English | WPRIM | ID: wpr-971365

ABSTRACT

OBJECTIVES@#Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms.@*METHODS@#Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions.@*RESULTS@#Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05).@*CONCLUSIONS@#Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.


Subject(s)
Animals , Mice , Dinitrochlorobenzene/metabolism , Skin/metabolism , Cytokines/metabolism , Interleukin-17/metabolism , Tumor Necrosis Factor-alpha/metabolism , Dermatitis, Allergic Contact/pathology , Dermatitis, Atopic/chemically induced , Signal Transduction , RNA, Messenger/metabolism , Mice, Inbred BALB C
2.
Article in Chinese | WPRIM | ID: wpr-1009416

ABSTRACT

Objective To investigate the effect of T cell immunoreceptor with Ig and ITIM domains (TIGIT) on the function of CD8+ T cells in the lungs of Plasmodium infected mice. Methods The lungs of the mice infected with Plasmodium yoelii were isolated, weighed and photographed after 12 days' infection. After dissolution, lung lymphocytes were isolated, counted and stained, and then the contents of CD8+ and TIGIT+CD8+ T cells were detected by flow cytometry. The expressions of L selectin (CD62L), CD69, programmed death 1 (PD-1), CD25, and C-X3-C motif chemokine receptor 1 (CX3CR1) on TIGIT+CD8+ T cells were detected by flow cytometry. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, the ability of TIGIT+CD8+T cells to secrete interferon γ(IFN-γ), interleukin 21 (IL-21), IL-4, IL-17, and IL-10 was detected. Results The body mass of mice with Plasmodium infection was reduced. The lungs became darker, and the ratio of the lung mass to body mass was significantly increased. Compared with the normal mice, the percentages and absolute quantity of CD8+ and TIGIT+CD8+ T cells in the lungs of the infected mice were significantly increased. The percentage of TIGIT+CD8+ T cells expressing CD62L in the infected group was significantly lower, while the percentage of the CD69, PD-1, and CX3CR1 cells were significantly higher than that of TIGIT+CD8+ T cells from the normal mice. The percentages of TIGIT+CD8+ T cells secreting IL-21, IL-4, IL-17 and IL-10 cells in the infected group were significantly lower. Conclusion The lung lesions from mice with Plasmodium infection are obvious, the numbers of TIGIT+CD8+ T cells increase, and these cells express a variety of activation-related molecules, but the ability to secrete cytokines is reduced.


Subject(s)
Animals , Mice , CD8-Positive T-Lymphocytes , Cytokines/metabolism , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-17/metabolism , Interleukin-4/metabolism , Lung/metabolism , Malaria/metabolism , Plasmodium yoelii/metabolism , Programmed Cell Death 1 Receptor/metabolism
3.
Chinese Journal of Hepatology ; (12): 504-508, 2023.
Article in Chinese | WPRIM | ID: wpr-986160

ABSTRACT

Objective: To investigate the effects of combined blockade of interleukin-33 (IL-33) and inducible co-stimulatory molecule (ICOS) on carbon tetrachloride-induced chronic liver fibrosis and imbalance of T helper lymphocyte subsets in mice. Methods: There were 40 BALB/c mice in each model and control group. Flow cytometry was used to determine the proportion of Th1/Th2/Th17 cells in the splenic lymphocyte suspension of mice, the expression levels of interferon γ, IL-4, and IL-17 in the splenic lymphocyte suspension of liver fibrosis mice after combined blockade of IL-33 and ICOS, and the pathological changes of liver histopathology in mice with liver fibrosis. Two independent sample t-test was used to compare data between groups. Results: Compared with the non-blocking group, the proportion of Th2 and Th17 cells in the IL-33/ICOS blocking group was significantly down-regulated (Th2: 65.96% ± 6.04% vs. 49.09% ± 7.03%; Th17: 19.17% ± 4.03% vs. 9.56% ± 2.03%), while the proportion of Th1 cells and Th1/Th2 ratio were up-regulated (Th1: 17.14% ± 3.02% vs. 31.93% ± 5.02%; Th1/Th2: 0.28 ± 0.06 vs. 0.62 ± 0.23), and the difference was statistically significant (t = 5.15, 6.03, 7.14, 4.28, respectively, with P < 0.05). After entering the chronic inflammation stage of liver fibrosis in mice (10 weeks), compared with the non-blocking group, the expression levels of IL-4 and IL-17 in the blockade group were significantly down-regulated [IL-4: (84.75 ± 14.35) pg/ ml vs. (77.88 ± 19.61) pg/ml; IL-17: (72.38 ± 15.13) pg/ml vs. (36.38 ± 8.65) pg/ml], while the expression of interferon γ was up-regulated [(37.25 ± 11.51) pg/ml vs. (77.88 ± 19.61) pg/ml], and the difference was statistically significant (t: IL-4: 4.71; IL-17: 5.84; interferon γ: 5.05, respectively, with P < 0.05). Liver histopathological results showed that hepatic necrosis, hepatic lobular structural disorder, and fibrous tissue hyperplasia were significantly lower in the blockade group than those in the non-blocking group at 13 weeks of liver fibrosis. Conclusion: Combined blockade of the ICOS signaling pathway and IL-33 can regulate Th2 and Th17 polarization, down-regulate the inflammatory response, and inhibit or prevent the occurrence and progression of fibrosis.


Subject(s)
Mice , Animals , Interferon-gamma/metabolism , Interleukin-17/metabolism , Interleukin-33/metabolism , Cytokines/metabolism , Carbon Tetrachloride , Th2 Cells , Interleukin-4/metabolism , Liver Cirrhosis/pathology , Th1 Cells , Th17 Cells/pathology , Immunity
4.
Article in Chinese | WPRIM | ID: wpr-986946

ABSTRACT

Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1β and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1β and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1β, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1β, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1β and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group(P=0.018,P<0.001,P=0.005, P=0.016) and the control group(all P<0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1β, and IL-18(r ralue was 0.643,0.650,0.629,respectively, all P<0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1β, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1β, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1β, and IL-18. The expressions of NLRP3, IL-1β and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1β and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.


Subject(s)
Female , Humans , Male , Young Adult , Adult , Middle Aged , Aged , Chronic Disease , Clinical Relevance , Inflammasomes , Interleukin-17/metabolism , Interleukin-18 , Nasal Polyps/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Rhinitis/metabolism , Sinusitis/metabolism
5.
Journal of Experimental Hematology ; (6): 1315-1321, 2023.
Article in Chinese | WPRIM | ID: wpr-1009987

ABSTRACT

OBJECTIVE@#To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL).@*METHODS@#Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits.@*RESULTS@#It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated.@*CONCLUSION@#Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.


Subject(s)
Humans , Leukemia, Promyelocytic, Acute/diagnosis , Cytokines/metabolism , Interleukin-10 , Interleukin-17/metabolism , Interleukin-6/metabolism , Interleukin-5/metabolism , Blood Coagulation Disorders , Ferritins , Tretinoin
6.
Journal of Integrative Medicine ; (12): 584-592, 2023.
Article in English | WPRIM | ID: wpr-1010967

ABSTRACT

OBJECTIVE@#To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation.@*METHODS@#Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.@*RESULTS@#EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.@*CONCLUSION@#Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.


Subject(s)
Animals , Mice , Interleukin-17/metabolism , Intercellular Adhesion Molecule-1 , Imiquimod/adverse effects , Tumor Necrosis Factor-alpha/metabolism , Ligands , Psoriasis/chemically induced , Keratinocytes , Inflammation/drug therapy , Chemokines/metabolism , Interferon-gamma/metabolism , Disease Models, Animal , Mice, Inbred BALB C
7.
Article in Chinese | WPRIM | ID: wpr-936325

ABSTRACT

OBJECTIVE@#To investigate the effect of triptolide (TPL) on inflammatory response and migration of fibroblast like synovial cells (FLS) in rheumatoid arthritis (RA-FLS) and the mechanism of circular noncoding RNA (circRNA) 0003353 for mediating this effect.@*METHODS@#We collected peripheral blood mononuclear cells (PBMCs) and serum samples from 50 hospitalized RA patients and 30 healthy individuals for detecting the expression of circRNA 0003353, immune and inflammatory indexes (ESR, CRP, RF, anti-CCP, IgA, IgG, IgM, C3, and C4) and DAS28 score. Cultured RA-FLS was treated with 10 ng/mL TPL and transfected with a circRNA 0003353 overexpression plasmid, and cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect the changes in the viability and migration of the cells. Enzyme-linked immunosorbent assay (ELISA) was used to examine the cytokines IL-4, IL-6, and IL-17, and real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the expression of circRNA 003353; Western blotting was used to detect the expressions of p-JAK2, pSTAT3, JAK2 and STAT3 proteins in the treated cells.@*RESULTS@#The expression of circRNA 0003353 was significantly increased in PBMCs from RA patients and showed a good performance in assisting the diagnosis of RA (AUC=90.5%, P < 0.001, 95% CI: 0.83-0.98). CircRNA 0003353 expression was positively correlated with ESR, RF and DAS28 (P < 0.05). Treatment with TPL significantly decreased the expression of circRNA 0003353, suppressed the viability and migration ability, decreased the expressions of IL-6 and IL-17, and increased the expression IL-4 in cultured RA-FLS in a time-dependent manner (P < 0.01). TNF-α stimulation of RA-FLS significantly increased the ratios of p-JAK2/JAK2 and p-STAT3/STAT3, which were obviously lowered by TPL treatment (P < 0.01). TPL-treated RA-FLS overexpressing circRNA 0003353 showed significantly increased cell viability and migration ability with decreased IL-4 expression and increased IL-6 and IL-17 expressions and ratios of p-JAK2/ JAK2 and p-STAT3/STAT3 (P < 0.01).@*CONCLUSION@#The expression of circRNA 0003353 is increased in PBMCs in RA patients and in RA-FLS. TPL treatment can regulate JAK2/STAT3 signal pathway and inhibit the inflammatory response and migration of RA-FLS through circRNA 0003353.


Subject(s)
Humans , Arthritis, Rheumatoid/pathology , Cells, Cultured , Diterpenes/pharmacology , Epoxy Compounds/pharmacology , Fibroblasts/pathology , Interleukin-17/metabolism , Interleukin-4/metabolism , Interleukin-6/metabolism , Janus Kinase 2/metabolism , Leukocytes, Mononuclear/metabolism , Phenanthrenes/pharmacology , RNA, Circular/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Synovial Membrane/pathology
8.
Article in Chinese | WPRIM | ID: wpr-936376

ABSTRACT

OBJECTIVE@#To explore the role of interleukin-17A (IL-17A) in renal epithelial- mesenchymal transition (EMT) in essential hypertensive nephropathy.@*METHODS@#Four-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (control group) were both randomized into 4 groups (n=5) for observation at 4, 6, 10 and 30 weeks of age. Blood pressure of the rats was monitored using a noninvasive tail artery blood pressure measurement instrument. The percentage of Th17 cells in the splenocytes was analyzed using flow cytometry. The mRNA and protein expression levels of IL-17A, iNOS, Arg-1, E-cadherin, and α-SMA in the kidneys of the rats were detected using RT-PCR and immunohistochemical staining, respectively, and plasma levels of IL-17A were regularly detected using ELISA.@*RESULTS@#At the age of 6 weeks, the SHRs began to show significantly higher blood pressure with greater Th17 cell percentage in the splenocytes and high renal expression and plasma level of IL-17A than WKY rats (P < 0.05 or P < 0.01). At 30 weeks, renal expression of E-cadherin mRNA and protein was significantly lower and the expression of Arg-1 mRNA and protein was significantly higher in SHR than in WKY rats (P < 0.01). Compared with the WKY rats, the SHRs showed significantly higher mRNA and protein expressions of iNOS at 6 and 10 weeks (P < 0.05 or 0.01) and higher α-SMA mRNA and protein expressions since 10 weeks of age (P < 0.05 or 0.01). In SHRs older than 10 weeks, renal IL-17A mRNA and protein expression levels were negatively correlated with those of E-cadherin (r=-0.731, P < 0.05; r=-0.827, P < 0.01) and positively correlated with those of α-SMA (r=0.658, P < 0.05; r=0.968, P < 0.01).@*CONCLUSION@#IL-17A is closely correlated with the progression of renal EMT in SHR and plays its role possibly by mediating M1/M2 polarization of renal infiltrating macrophages.


Subject(s)
Animals , Rats , Blood Pressure , Cadherins/metabolism , Epithelial-Mesenchymal Transition , Hypertension , Interleukin-17/metabolism , Kidney , RNA, Messenger/metabolism , Rats, Inbred SHR , Rats, Inbred WKY
9.
Article in Chinese | WPRIM | ID: wpr-927420

ABSTRACT

OBJECTIVE@#To observe the effect of fire needling on psoriasis-like lesion and the signal transducer and activator of transcription 3 (STAT3) pathway in mice and compare the therapeutic effect between different interventions of fire needling therapy (surrounding technique of fire needling, fire needling at "Dazhui" [GV 14] and "Zusanli" [ST 36]).@*METHODS@#Thirty male BALB/c mice were randomized into a blank group, a model group, a dexamthasone group, a surrounding technique group and an acupoint group, 6 mice in each one. Except the blank group, the mice in the rest groups were established as psoriasis-like lesion model by topical application with imiquimod cream, once daily, consecutively for 8 days. From day 4 to day 8, in the dexamthasone group, gastric infusion with 0.2 mL dexamthasone was administered, once daily. On day 4, 6 and 8, in the surrounding technique group, fire needling was exerted around the skin lesion; and fire needling was applied to "Dazhui" (GV 14) and "Zusanli" (ST 36) in the acupoint group, once a day. The changes in skin lesion on the dorsal parts of mice were observed in each group to score the psoriasis area and severity index (PASI). Using HE staining, the dermal morphological changes and epidermal thickness were observed in the mice of each group. The positive expression of proliferating cell-associated antigen Ki-67 was determined by immunofluorescence. Immunohistochemistry method was used to determine the expressions of , and T cells of skin tissue in each group. Using real-time PCR, the expressions of interleukin (IL)-17, IL-22, tumor necrosis factor α(TNF-α) mRNA were determined. Western blot method was adopted to determine the protein expressions of STAT3 and p-STAT3 in skin tissue in each group.@*RESULTS@#Compared with the blank group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all increased in the mice of the model group (P<0.01). Except for the erythema scores of the dexamethasone group and the surrounding technique group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all decreased in each intervention group as compared with the model group (P<0.01). The infiltration scores and the total scores in the dexamethasone group and the acupoint group were lower than those in the surrounding technique group respectively (P<0.01, P<0.05). In comparison with the blank group, Ki-67 positive cell numbers and the numbers of , and T cells in skin tissue were increased in the mice of the model group (P<0.01). Ki-67 positive cell numbers and the numbers of , and T cells were reduced in each intervention group as compared with the model group (P<0.01), and the numbers of and T cells in the acupoint group were less than the surrounding technique group (P<0.01). Compared with the blank group, the mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all increased in the model group (P<0.01). The mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all decreased in each intervention group as compared with the model group (P<0.01, P<0.05). The mRNA expressions of IL-17, IL-22 and TNF-α in the acupoint group, as well as mRNA expression of IL-17 in the surrounding technique group were all lower than the dexamethasone group (P<0.01), while, the mRNA expression of IL-22 in the acupoint group was lower than the surrounding technique group (P<0.01).@*CONCLUSION@#Fire needling therapy improves skin lesion severity in imiquimod induced psoriasis-like lesion of the mice, which is probably related to the inhibition of STAT3 pathway activation and the decrease of Th17 inflammatory factors expression. The systemic regulation of fire needling at "Dazhui" (GV 14) and "Zusanli" (ST 36) is superior to the local treatment.


Subject(s)
Animals , Male , Mice , Dexamethasone/therapeutic use , Imiquimod/metabolism , Interleukin-17/metabolism , Ki-67 Antigen/metabolism , Mice, Inbred BALB C , Psoriasis/drug therapy , RNA, Messenger/metabolism , STAT3 Transcription Factor/pharmacology , Skin/pathology , Tumor Necrosis Factor-alpha/metabolism
10.
Rio de Janeiro; s.n; 2021. 74 p. ilus, Tab.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1399121

ABSTRACT

O líquen plano oral (LPO) é uma condição imuno-inflamatória mucocutânea crônica que ainda possui etiologia e patogênese desconhecidas. Estudos mostrando a participação de citocinas no LPO, em especial, interleucinas (IL)-6, IL-17 e IL-18, são escassos, assim como a correlação das características clínicas e histológicas das lesões de LPO com a presença destes mediadores inflamatórios. Todas as lesões de LPO e de lesões liquenoides orais (LLO) foram revisadas a partir do arquivo do laboratório de Patologia Bucal da Faculdade de Odontologia da Universidade do Estado do Rio de Janeiro e as características clínico-patológicas dos casos foram analisadas. Foram selecionados 40 casos de LPO para realização adicional de reações imuno-histoquímicas para IL-6, IL-17 e IL-18. A amostra total foi composta por 221 casos e mostrou que o LPO apresentou predileção por mulheres adultas, mais frequentemente acometidas pelo padrão reticular e com lesões localizadas predominantemente na mucosa jugal. Os 40 casos selecionados para a avaliação imuno-histoquímica incluíram pacientes com média de idade de 53 anos, sem predileção por gênero, e com lesões localizadas preferencialmente na mucosa jugal (85%), na gengiva/mucosa alveolar (47%) e na língua (42%). Quanto ao padrão clínico, 14 pacientes (35%) mostravam lesões exclusivamente reticulares e 26 (65%) mostravam lesões reticulares associadas a lesões atrófico-erosivas. Sintomas foram relatados por 53% dos pacientes e incluíram principalmente ardência e desconforto local. A análise histológica mostrou que o epitélio das lesões mostrava espessura normal, atrófica ou hiperplásica em, respectivamente, 17 (43%), 9 (22%) e 14 (35%) casos. A presença de hiperqueratose foi observada em 21 casos (53%) e exocitose de linfócitos T CD4+ e T CD8+ estava presente em, respectivamente, 17 (42%) e 30 (75%) casos. A análise imuno-histoquímica revelou que a IL-6 foi, de forma geral, a mais expressa, tanto no epitélio, quanto no conjuntivo. A expressão de IL-17 se mostrou intensa no tecido conjuntivo, em 40% dos casos. A IL-18 mostrou intensidade mais frequente leve/moderada tanto no epitélio (40%), quanto no tecido conjuntivo (45%). A presença de exocitose mostrou relação com a maior expressão das ILs e a expressão de IL-17 foi maior no epitélio mostrando hiperqueratose. Os resultados do presente estudo mostraram que as características clínicas das lesões de LPO e de LLO são distintas e podem ser utilizadas para diferenciação entre as duas entidades. Os achados histológicos e imunohistoquímicos sugerem que as ILs estudadas mostram-se mais presentes quando há exocitose linfócitos T CD4+ e T CD8+ e que sua expressão pode ter relação com as alterações epiteliais encontradas no LPO, participando da patogênese e da modulação da expressão da doença.


Oral lichen planus (OLP) is a chronic immunoinflammatory mucocutaneous condition of unknown etiology and pathogenesis. Studies focusing on the presence of cytokines in OLP, especially interleukin (IL)-6, IL-17 and IL-18, are scarce, as well as the correlation of clinical and histological characteristics with the presence of inflammatory mediators. All lesions diagnosed as OLP and oral lichenoid lesions (OLL) were reviewed from the files of the Oral Pathology laboratory, Dental School, Rio de Janeiro State University, and their clinicopathological characteristics were analyzed. Forty cases diagnosed as OLP were selected for additional immunohistochemical reactions directed against IL-6, IL-17 e IL-18. The total sample was composed by 221 cases and showed that OLP presented a predilection for adult females, mostly affected by lesions with the reticular pattern and located in the buccal mucosa. The 40 cases selected for the immunohistochemical reactions included patients with a mean age of 53 years, with no gender predilection, and with lesions located mostly in the buccal mucosa (85%), gingiva/alveolar mucosa (47%) and tongue (42%). The clinical pattern showed reticular lesions in 14 patients (35%) and reticular and atrophic/erosive lesions in 26 patients (65%). Symptoms were reported by 53% of the patients and included mostly burning sensation and local discomfort. Histological analysis showed that the epithelial thickness was normal, atrophic, or hyperplastic in, respectively, 17 (43%), 9 (22%) and 14 (35%) cases. The presence of hyperkeratosis was observed in 21 cases (53%), and exocytosis of T CD4+ and T CD8+ lymphocytes was present in, respectively, 17 (42%) and 30 (75%) cases. Immunohistochemical analysis showed that, in general, IL-6 was the most expressed IL both in epithelium and connective tissue. IL-17 expression was considered intense in the connective tissue from 40% of the cases. IL-18 expression was considered mostly mild/moderate both in epithelium (40% of the cases) and connective tissue (45% of the cases). The presence of exocytosis was associated with a higher expression of the ILs and expression of IL-17 was higher in epithelium showing hyperkeratosis. The results from the present study showed that the clinical characteristics of OLP and OLL are distinct and can be useful in differentiating these two diagnostic entities. The histological and immunohistochemical features suggest that the studied ILs are more expressed when there is exocytosis of both T CD4+ and T CD8+ lymphocytes. Expression of the ILs can be associated with the epithelial alterations encountered in OLP, participating in the pathogenesis and modulating the expression of the disease.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Interleukin-6/metabolism , Lichen Planus, Oral/metabolism , Inflammation Mediators/metabolism , Interleukin-17/metabolism , Interleukin-18/metabolism , Immunohistochemistry , Retrospective Studies , Lichen Planus, Oral/pathology
11.
Journal of Forensic Medicine ; (6): 40-44, 2016.
Article in Chinese | WPRIM | ID: wpr-984040

ABSTRACT

OBJECTIVE@#To explore the correlation between the interleukin-17 (IL-17) level of peripheral blood and aggression of bipolar mania.@*METHODS@#Thirty-six patients of bipolar mania were selected as experimental group by DSM-IV-TR and received treatment with quetiapine and lithium. Thirty-six healthy volunteers with similar age and gender were selected as control group. The level of IL-17 at baseline in each group and the level of IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were detected by ELISA.@*RESULTS@#The level of IL-17 in experimental group at baseline, after treatment for 2 and 4 weeks were all significantly higher than that in control group. After 8 weeks treatment, there was no significant difference between the two groups (P > 0.05). After 2, 4 and 8 weeks treatment, the total score and aggression score of Young Mania Rating Score (YMRS) were significantly lower than the baseline level (P < 0.05). In experimental group, the level of IL-17 was positively correlated with the two scores of YMRS at baseline (P < 0.05).@*CONCLUSION@#Bipolar mania may be related to the up-regulation of IL-17. The level of IL-17 is related to the severity of manic symptoms at baseline, especially aggression symptom.


Subject(s)
Humans , Aggression/drug effects , Antipsychotic Agents/therapeutic use , Biomarkers/blood , Bipolar Disorder/drug therapy , Case-Control Studies , Diagnostic and Statistical Manual of Mental Disorders , Double-Blind Method , Interleukin-17/metabolism , Lithium Compounds/therapeutic use , Quetiapine Fumarate/therapeutic use , Treatment Outcome
12.
Gut and Liver ; : 381-387, 2015.
Article in English | WPRIM | ID: wpr-203888

ABSTRACT

BACKGROUND/AIMS: Microscopic colitis is characterized by chronic watery diarrhea with specific pathological changes that can be diagnosed by microscopic examination. We performed immunohistochemical analysis of proinflammatory cytokines to investigate the pathogenic mechanism of microscopic colitis. METHODS: This study consisted of six patients with lymphocytic colitis, six patients with collagenous colitis, and six patients with functional diarrhea but normal pathology. We performed an immunohistochemical analysis of the colonic mucosal biopsies to assess the expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-kappaB, interferon-gamma, inducible nitric oxide synthase, and tumor necrosis factor-alpha. We compared the quantity score of immunohistochemical staining among the groups. RESULTS: The microscopic colitis group showed significantly higher expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-kappaB, and interferon-gamma compared with the control group. Cytokine expression was similar between collagenous colitis and lymphocytic colitis. However, the expression of cyclo-oxygenase-2 was higher in collagenous colitis. CONCLUSIONS: Proinflammatory cytokines, including interleukin-17 and interferon-gamma, are highly expressed in microscopic colitis. The expression of cyclo-oxygenase-2 was higher in collagenous colitis than in lymphocytic colitis. This study is the first on interleukin-17 expression in microscopic colitis patients.


Subject(s)
Humans , Biopsy , Colitis, Microscopic/metabolism , Colon/pathology , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Diarrhea/metabolism , Interferon-gamma/metabolism , Interleukin-17/metabolism , Intestinal Mucosa/pathology , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Tumor Necrosis Factor-alpha/metabolism
13.
Article in English | WPRIM | ID: wpr-51380

ABSTRACT

PURPOSE: This study investigated interleukin (IL)-17-secreting cell involvement in sterile inflammation, and evaluated the effect of mesenchymal stem cells (MSCs) on IL-17-secreting cell immunologic profiling. METHODS: Twenty mice were sacrificed at time points of 6 hours, 1 day, 1 week, and 3 weeks (each group, n = 5) after the cornea was chemically injured with 0.5N NaOH; IL-17 changes in the cornea were evaluated using enzyme-linked immunosorbent assay. Further, IL-17 secreting cells were assessed in the cervical lymph nodes by a flow cytometer. Rat MSCs were applied intraperitoneally in a burn model (n = 10), IL-17-secreting T helper 17 (Th17) cell and non-Th17 cell changes were checked using a flow cytometer in both cornea and cervical lymph nodes at 1week, and compared with those in the positive control (n = 10). RESULTS: IL-17 was highest in the cornea at 1 week, while, in the cervical lymph nodes, IL-17-secreting cells showed early increase at 6 hours, and maintained the increase through 1 day to 1 week, and levels returned to the basal level at 3 weeks. Specifically, the non-Th17 cells secreted IL-17 earlier than the Th17 cells. When the MSCs were applied, IL-17 secretion was reduced in CD3(+)CD4(-)CD8(-), CD3(+)CD4(+)CD8(-), and CD3(+) CD4(-)CD8(+) cells of the cervical lymph nodes by 53.7%, 43.8%, and 50.8%, respectively. However, in the cornea, IL-17 secretion of CD3(+)CD4(-)CD8(-) cells was completely blocked. CONCLUSIONS: The results indicated that both IL-17-secreting non-Th17 and Th17 cells were involved in the chemical burn model, and MSCs appeared to mainly modulate non-Th17 cells and also partially suppress the Th17 cells.


Subject(s)
Animals , Male , Mice , Burns, Chemical/immunology , Cells, Cultured , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Eye Burns/immunology , Flow Cytometry , Immunity, Cellular , Interleukin-17/metabolism , Mesenchymal Stem Cells/immunology , Mice, Inbred C57BL
14.
Indian J Dermatol Venereol Leprol ; 2013 Nov-Dec; 79(6): 772-776
Article in English | IMSEAR | ID: sea-154677

ABSTRACT

Background: Combating Mycobacterium leprae is known to be via T-helper1 response. However, other T-helper effector cells; T-helper17 and T-helper2; play a role, particularly in the context of disease type. Aims: We aimed to evaluate serum levels of interleukin (IL)-17 (T-helper17 cytokine) and IL-4 (T-helper2 cytokine) in untreated patients with different types of leprosy, compared to controls. Methods: Using enzyme-linked immunosorbent assay, serum IL-17 and IL-4 levels were estimated in 43 leprotic patients and 43 controls. Patients were divided into six groups; tuberculoid, borderline cases, lepromatous, erythema nodosum leprosum (ENL), type 1 reactional leprosy, and pure neural leprosy. Patients were also categorized according to bacillary load and the presence or absence of reactions. Results: Serum IL-17 was signifi cantly lower in cases (4-61.5 pg/mL; median 19), compared to controls (26-55 pg/mL; median 36) (P < 0.001), and was signifi cantly lower in each type of leprosy compared to controls, with the lowest level in lepromatous leprosy (4-61.5 pg/mL; median 12.5). Signifi cantly elevated serum IL-4 was found in patients (1.31-122.4 pg/mL; median 2.31) compared to controls (1.45-5.72 pg/mL; median 2.02) (P = 0.008), with the highest level among lepromatous leprosy patients (2-87.2 pg/mL; median 28.9), and the lowest in type 1 reactional leprosy (1.4-2.5 pg/mL; median 1.87) (P = 0.006). Conclusion: Defective secretion of IL-17 is related to disease acquisition as well as progression toward lepromatous pole in leprosy patients. The overproduction of IL-4 in patients with lepromatous leprosy may infer their liability to develop ENL. Nevertheless, the small number of the studied population is a limitation.


Subject(s)
Adolescent , Adult , Aged , Biomarkers/blood , Comprehension , Disease Progression , Female , Humans , Interleukin-17/blood , Interleukin-17/metabolism , Interleukin-4/blood , Leprosy/blood , Leprosy/diagnosis , Leprosy/pathology , Male , Middle Aged , Young Adult
15.
Yonsei Medical Journal ; : 183-188, 2013.
Article in English | WPRIM | ID: wpr-66223

ABSTRACT

PURPOSE: Our aim was to determine the effects of infliximab on bone mineral metabolism in rheumatoid arthritis (RA) patients and analyze the relationship between inflammatory markers of acute phase thought to play a major role in bone remodeling. MATERIALS AND METHODS: 36 patients with established RA were investigated. All patients underwent physical examination and blood and urinary analysis at baseline, 2 weeks, 14 weeks, 6 months and 12 months after the initiation of treatment. The serum levels of: tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor alpha receptor 1 (TNFR1), TNFR2, interleukin 6 (IL-6), IL-17, IL-23 and markers of bone remodeling such as osteocalcin (BGP), deoxypyridynoline (Dpd), and N-telopeptide of type I collagen (NTx) were measured by ELISA. RESULTS: The results showed significant decrease of all the above cytokines levels in RA patients in comparison with those after 2 weeks of treatment. After 6 months, the markers of bone formation and resorption decreased compared to baseline values. We found positive correlation between the levels of NTx and the levels of IL-6, IL-17 and TNFR1, and between the levels of Dpd and IL-6 and Dpd and TNFR2, whereas negative correlation between BGP and IL-23. After 12 months the positive association was found at the BGP level and IL-6 as well as Dpd and the level of IL-6. We also observed a positive relation between Dpd and TNF-alpha and negative between BGP and TNFR1. CONCLUSION: We suggest that infliximab treatment may limit the risk of osteoporosis in RA patients.


Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/blood , Biomarkers/metabolism , Bone Remodeling/drug effects , Bone Resorption , Cytokines/metabolism , Gene Expression Regulation , Interleukin-17/metabolism , Interleukin-6/metabolism , Osteoporosis/complications , Receptors, Tumor Necrosis Factor, Type I/metabolism
16.
Article in English | WPRIM | ID: wpr-147328

ABSTRACT

Myeloid-related protein (MRP)8/MRP14 is an endogenous Toll-like receptor 4 (TLR4) ligand and is abundant in synovial fluid (SF) of rheumatoid arthritis (RA) patients. Belonging to damage-associated molecular patterns, it amplifies proinflammatory mediators and facilitates a wide range of inflammatory and autoimmune diseases. Interleukin (IL)-17-producing T-helper (Th)17 cells have a crucial role in RA pathogenesis, and IL-6 is the key factor promoting Th17 differentiation. We investigated whether the level of MRP8/MRP14 is positively associated with IL-6 and IL-17 levels in RA SF and found that MRP8/MRP14 level had a significant correlation with IL-6 and IL-17 levels in RA SF. We also observed that MRP8-induced IL-17 production by peripheral blood mononuclear cells but MRP14 did not. Upon stimulation with MRP8, IL-6 production was enhanced by RA fibroblast-like synoviocytes (FLS) and was further elevated by coculturing RA FLS with activated CD4+ T cells. Moreover, we demonstrated that MRP8-activated IL-6 production by RA FLS promoted differentiation of Th17 cells using the coculture system consisting of CD4+ T cells and RA FLS. In addition, IL-6 blockade attenuated Th17 polarization of CD4+ T cells in the cocultures. Inhibitor studies revealed that MRP8 increased IL-6 production in RA FLS via TLR4/phosphoinositide 3-kinase/nuclear factor-kappaB and mitogen-activated protein kinase signaling pathways. Our results show that MRP8 has a crucial role in stimulating IL-6 expression by RA FLS, and subsequently promotes Th17 differentiation in RA, suggesting that neutralizing MRP8 level in RA synovium may be an effective therapeutic strategy in RA treatment.


Subject(s)
Adult , Aged , Humans , Middle Aged , ATP-Binding Cassette Transporters/metabolism , Arthritis, Rheumatoid/pathology , CD4-Positive T-Lymphocytes/metabolism , Calgranulin B/metabolism , Cell Differentiation/immunology , Fibroblasts/metabolism , Inflammation Mediators/metabolism , Interleukin-17/metabolism , Interleukin-6/biosynthesis , Signal Transduction/immunology , Synovial Fluid/cytology , Synovial Membrane/metabolism , Th17 Cells/pathology , Toll-Like Receptor 4/metabolism , Up-Regulation
17.
Article in English | WPRIM | ID: wpr-213998

ABSTRACT

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback.


Subject(s)
Animals , Mice , Aspirin/pharmacology , Cell Polarity/drug effects , Feedback, Physiological/drug effects , Interferon-gamma/deficiency , Interleukin-17/metabolism , Interleukin-6/biosynthesis , Lipopolysaccharides/pharmacology , Lung/drug effects , Mice, Inbred C57BL , Pneumonia/drug therapy , Th17 Cells/drug effects , Transforming Growth Factor beta1/pharmacology
18.
Article in English | WPRIM | ID: wpr-119839

ABSTRACT

White fat cells secrete adipokines that induce inflammation and obesity has been reported to be characterized by high serum levels of inflammatory cytokines such as IL-6 and TNF-alpha. Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis, but the relationship between RA and obesity is controversial. We made an obese inflammatory arthritis model: obese collagen-induced arthritis (CIA). C57BL/6 mice were fed a 60-kcal high fat diet (HFD) from the age of 4 weeks and they were immunized twice with type II collagen (CII). After immunization, the obese CIA mice showed higher arthritis index scores and histology scores and a more increased incidence of developing arthritis than did the lean CIA mice. After treatment with CII, mixed lymphocyte reaction also showed CII-specific response more intensely in the obese CIA mice than lean CIA. The anti-CII IgG and anti-CII IgG2a levels in the sera of the obese CIA mice were higher than those of the lean CIA mice. The number of Th17 cells was higher and the IL-17 mRNA expression of the splenocytes in the obese CIA mice was higher than that of the lean CIA mice. Obese CIA mice also showed high IL-17 expression on synovium in immunohistochemistry. Although obesity may not play a pathogenic role in initiating arthritis, it could play an important role in amplifying the inflammation of arthritis through the Th1/Th17 response. The obese CIA murine model will be an important tool when we investigate the effect of several therapeutic target molecules to treat RA.


Subject(s)
Animals , Humans , Mice , Adipokines/immunology , Arthritis, Experimental/genetics , Cell Differentiation/genetics , Collagen Type II/administration & dosage , Disease Models, Animal , Gene Expression , Inflammation/chemically induced , Interleukin-17/metabolism , Interleukin-6/blood , Joints/immunology , Mice, Inbred C57BL , Obesity/genetics , Th17 Cells/immunology , Tumor Necrosis Factor-alpha/blood
19.
IBJ-Iranian Biomedical Journal. 2011; 15 (1,2): 1-5
in English | IMEMR | ID: emr-129770

ABSTRACT

During antigen capture and processing, mature dendritic cells [DC] express large amounts of peptide-MHC complexes and accessory molecules on their surface. DC are antigen-presenting cells that have an important role in tolerance and autoimmunity. The transforming growth factor-beta 1 [TGF-beta1] cytokine has a regulatory role on the immune and non-immune cells. The aim of this study is to evaluate the effect of TGF-beta1 on the induction of human leukocyte antigen-G [HLA-G] expression on the DC which is derived from monocyte. Methods: In this study, we evaluated the effect of TGF-beta1 in induction HLA-G expression on the monocyte-derived DC by flowcytometry and then CD4[+] T cell proliferative responses in the presence of DC-treated TGF-[beta1] was studied. Results: The results of this study showed that DC bearing HLA-G down-regulated activation of CD4[+] T cells and production of IL-6 and IL-17 in comparison with control [P<0.05]. Conclusion: It is concluded that TGF-beta1 has an important regulatory role in CD4[+] T cell proliferation by increasing HLA-G on DC and these cells can probably prevent unexpected immune responses in vivo


Subject(s)
Humans , /pharmacology , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , Dendritic Cells/drug effects , Dendritic Cells/immunology , B7-2 Antigen/metabolism , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Interleukin-17/metabolism , Interleukin-6/metabolism
20.
Article in English | WPRIM | ID: wpr-155753

ABSTRACT

The aim of this study was to evaluate whether the Th17 and Treg cell infiltration into allograft tissue is associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens were immunostained for FOXP3 and IL-17. The allograft function was assessed at biopsy by measuring serum creatinine (Scr) concentration, and by applying the modified diet in renal disease (MDRD) formula, which provides the estimated glomerular filtration rate (eGFR). The severity of allograft tissue injury was assessed by calculating tissue injury scores using the Banff classification. The average numbers of infiltrating Treg and Th17 cells were 11.6 +/- 12.2 cells/mm2 and 5.6 +/- 8.0 cells/mm2, respectively. The average Treg/Th17 ratio was 5.6 +/- 8.2. The Treg/Th17 ratio was significantly associated with allograft function (Scr and MDRD eGFR) and with the severity of interstitial injury and tubular injury (P < 0.05, all parameters). In separate analyses of the number of infiltrating Treg and Th17 cells, Th17 cell infiltration was significantly associated with allograft function and the severity of tissue injury. By contrast, Treg cell infiltration was not significantly associated with allograft dysfunction or the severity of tissue injury. The results of this study show that higher infiltration of Th17 cell compared with Treg cell is significantly associated with the severity of allograft dysfunction and tissue injury.


Subject(s)
Humans , Acute Disease , Creatinine/metabolism , Forkhead Transcription Factors/metabolism , Graft Rejection/etiology , Immunoenzyme Techniques , Interleukin-17/metabolism , Kidney Transplantation/adverse effects , Retrospective Studies , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Transplantation, Homologous
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