Study on mechanisms of Th17/Treg imbalance in patients with cystic echinococcosis based on miRNA expression profiles / 中国血吸虫病防治杂志

OBJECTIVE@#To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis.@*METHODS@#Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched.@*RESULTS@#A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways.@*CONCLUSIONS@#Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.

Moxibustion regulates T-regulatory/T-helper 17 cell balance by modulating the microRNA-221/suppressor of cytokine signaling 3 axis in a mouse model of rheumatoid arthritis / 中西医结合学报

OBJECTIVE@#Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model.@*METHODS@#A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay.@*RESULTS@#It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.@*CONCLUSION@#Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.

Relationship between the Expression of miRNA181a-5p and the Imbalance of Treg/Th17 in Primary Immune Thrombocytopenia / 中国实验血液学杂志

OBJECTIVE@#To investigate the role of relationship between the expression of miRNA181a-5p and imbalance of Treg/Th17 in the pathogenesis of primary immune thrombocytopenia(ITP), which contributes to clarify the mechanism of T cell immune imbalance in ITP patients.@*METHODS@#Peripheral blood was collected from 37 ITP patients, concluding 21 untreated patients and 16 effectively treated patients, and 19 healthy controls; Peripheral blood mononuclear cells (PBMC) were isolated and the expression of miRNA181a-5p and Notch1 was analyzed by RT-PCR. The proportion of Th17 subsets and Treg cells in the peripheral circulation was detected by flow cytometer (FCM). Clinical data of ITP group was collected, including age, platelet count and disease course.@*RESULTS@#The expression of miR-181a-5p was significantly decreased in ITP group than that of healthy control group (P＜0.01). After effective treatment, the expression of miR-181a-5p was significantly higher than that of ITP group (P＜0.05), but still significantly lower than that of healthy control group (P＜0.01); The expression of Notch1 was significantly increased in ITP group and effectively treated group than that of healthy control group (P＜0.01). There was no significant difference in proportion of Treg cells in ITP group, effectively treated group and healthy control group (P＞0.05). The proportion of Th17 subsets in ITP group was significantly increased than that of healthy control group (P＜0.05), while the ratio of Treg/Th17 was significantly decreased (P＜0.05). There was a positive correlation between the expression of miR-181a-5p and ratio of Treg/Th17 in ITP group (r=0.555).@*CONCLUSION@#The expression of miR-181a-5p is significantly decreased in ITP patients, which is closely related to the imbalance of Treg/Th17 cells. After effective treatment, the expression of miR-181a-5p can be significantly corrected, but still failed to reach the level of healthy people. While the expression of Notch1 is significantly increased in ITP patients, and could not reach the level of healthy people after effective treatment.

Expression of miR-106b-5p in children with primary immune thrombocytopenia and its correlation with T cells / 中国当代儿科杂志

OBJECTIVES@#To study the expression level of plasma miR-106b-5p in primary immune thrombocytopenia (ITP) and its correlation with the levels of T helper 17 cell (Th17) and regulatory T cell (Treg) and the Th17/Treg ratio.@*METHODS@#A total of 79 children with ITP (ITP group) and 40 healthy children (control group) were selected as subjects. According to the treatment response, the 79 children with ITP were divided into three groups: complete response (n=40), partial response (n=18), and non-response (n=21). Quantitative real-time PCR was used to measure the expression level of miR-106b-5p. Flow cytometry was used to measure the frequencies of Th17 and Treg, and the Th17/Treg ratio was calculated. The correlation of the expression level of plasma miR-106b-5p with the frequencies of Th17 and Treg and the Th17/Treg ratio was analyzed.@*RESULTS@#Compared with the control group, the ITP group had significantly higher levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly lower level of Treg (P<0.05). After treatment, the ITP group had significant reductions in the levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significant increase in the level of Treg (P<0.05). Compared with the partial response and non-response groups, the complete response group had significantly lower levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly higher level of Treg (P<0.05). The correlation analysis showed that in the children with ITP, the expression level of plasma miR-106b-5p was positively correlated with the Th17 level and the Th17/Treg ratio (r=0.730 and 0.816 respectively; P<0.001) and was negatively correlated with the Treg level (r=-0.774, P<0.001).@*CONCLUSIONS@#A higher expression level of miR-106b-5p and Th17/Treg imbalance may be observed in children with ITP. The measurement of miR-106b-5p, Th17, Treg, and Th17/Treg ratio during treatment may be useful to the evaluation of treatment outcome in children with ITP.

Effects of astragaloside Ⅳ on inflammatory response and percentage of peripheral blood Th17 cells in mice with ulcerative colitis / 中国中药杂志

This study aimed to investigate the anti-inflammatory effect of astragaloside Ⅳ in mice with ulcerative colitis(UC) and its effect on the percentage of peripheral blood T helper(Th17) cells. Following the establishment of UC mouse model with 2% sodium dextran sulfate(DSS), mice in the positive control group and low-and high-dose astragaloside Ⅳ groups were treated with corresponding drugs by gavage. Disease activity index(DAI) was calculated, and serum interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), and transforming growth factor-β(TGF-β) levels were assayed by ELISA. The pathological changes in colon tissue were observed by HE staining, and Th17/regulatory T cells(Treg) ratio in the peripheral blood was determined by flow cytometry. Western blot was conducted for detecting the relative protein expression levels of forkhead box protein P3(Foxp3) and retinoic acid-related orphan nuclear receptor γT(ROR-γt). The findings demonstrated that in normal mice, the colonic structure was intact. The goblet cells were not reduced and the glands were neatly arranged, with no mucosal erosion, bleeding, or positive cell infiltration. In the model group, the colonic mucosal structure was seriously damaged, manifested as disordered arrangement or missing of glands, vascular dilatation, congestion, and massive inflammatory cell infiltration. The pathological injury of colon tissue was alleviated to varying degrees in drug treatment groups. Compared with the normal group, the model group exhibited elevated percentage of Th17 cells, increased IL-17 and TNF-α content, up-regulated relative ROR-γt protein expression, lowered TGF-β, reduced percentage of Treg cells, and down-regulated relative Foxp3 protein expression. The comparison with the model group showed that DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the positive control group, low-dose astragaloside Ⅳ group, and high-dose astragaloside Ⅳ group were decreased, while TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression were increased. The DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the low-dose astragaloside Ⅳ group were higher than those in the positive control group, whereas the content of TGF-β, percentage of Treg cells, and relative Foxp3 protein expression were lower. DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, relative ROR-γt protein expression in the high-dose astragaloside Ⅳ group declined in contrast to those in the low-dose astragaloside Ⅳ group, while the TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression rose. There was no significant difference between the positive control group and the high-dose astragaloside Ⅳ group. Astragaloside Ⅳ is able to inhibit inflammatory response and diminish the percentage of Th17 cells in mice with UC.

Effect of Astragali Radix-Curcumae Rhizoma compatibility combined with 5-fluorouracil on Th17/Treg balance and tumor-related mRNA and protein expression in orthotopic xenograft model mice of CT26.WT colorectal carcinoma / 中国中药杂志

Astragali Radix-Curcumae Rhizoma(AR-CR) is a combination commonly used in the clinical treatment of tumors. Based on the T helper 17(Th17)/regulatory T cell(Treg) balance, the present study explored the possible mechanism of AR-CR combined with 5-fluorouracil(5-FU) on the tumor growth of orthotopic xenograft model mice of colorectal carcinoma. Ninety male BALB/c mice were randomly divided into nine groups, i.e., a blank group, a model group, a 5-FU group, high-, medium-, and low-dose AR-CR(2∶1) groups, and high-, medium-, and low-dose AR-CR+5-FU groups, with 10 mice in each group. The orthotopic xenograft model of CT26.WT colorectal carcinoma was induced in mice except those in the blank group. Twenty-four hours after the ope-ration, mice in the blank group and the model group received normal saline by gavage(10 mL·kg~(-1), once per day), and those in the 5-FU group received 5-FU by intraperitoneal injection(25 mg·kg~(-1), once every other day). Mice in the AR-CR groups received AR and CR decoctions by gavage(12, 6, and 3 g·kg~(-1), once a day) and those in the combination groups received AR and CR decoctions and 5-FU(doses and administration methods were the same as above). After intervention for three weeks, all mice were sacrificed and tumor tissues were collected. The tumor mass was weighed and the average tumor weight was calculated. The changing trend of Th17/Treg(%) in the CD4~+T lymphocytes of the spleen tissues of the mice in each group was detected. The mRNA expression in the blood and protein expression in the tumor tissues of transforming growth factor-β(TGF-β), tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), Smad4, N-cadherin, matrix metalloproteinase-7(MMP-7) were detected. The experimental results revealed that compared with the model group, the groups with drug intervention showed reduced tumor mass(P<0.01), decreased CD4~+IL-17~+ in the spleen tissues to varying degrees(P<0.001), and increased proportion of CD4~+Foxp3~+(P<0.001 or P<0.05), indicating that Th17/Treg maintained dynamic balance, and the effect of the combination groups was predominant. Additionally, the mRNA expression in the blood and protein expression in the tumor tissues of TGF-β, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 declined to varying degrees in a dose-dependent manner(P<0.01 or P<0.001). The AR-CR combined with 5-FU can inhibit the tumor growth of orthotopic xenograft model mice of CT26.WT colorectal carcinoma. The mechanism may be related to maintenance of Th17/Treg dynamic balance in the body and down-regulation of TGF-β, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 expression.

Tanshinone IIA ameliorates myocardial ischemia/reperfusion injury in rats by regulation of NLRP3 inflammasome activation and Th17 cells differentiation

Purpose: Tanshinone IIA is a well-known lipophilic active constituent refined from traditional Chinese medicines, danshen. It has been previously demonstrated to possess various biological properties, including anti-inflammatory, antioxidant, promoting angiogenesis effect and so on. However, the mechanism of tanshinone IIA on myocardial ischemia-reperfusion injury (MI/RI) remains unclear. In this study, we investigated the effect of tanshinone IIA on MI/RI. Methods: MI/RI rat models were set up. Echocardiographic evaluation and hematoxylin and eosin staining were performed to analyze the cardiac function and morphology of MI/RI. Western blot was conducted for the detection of protein expression of pyrin domain containing 3 (NLRP3) and caspase-1 in heart tissues. Flow cytometry and real-time polymerase chain reaction were used for the detection of proinflammatory cytokines and Th17 cells differentiation. Results: We found that tanshinone IIA alleviated the myocardial damage of MI/RI, ameliorated the overall and local inflammatory reaction, and produced a cardioprotective effect by inhibiting of NLRP3 inflammasome activation and Th17/Treg cells differentiation. Conclusions: Our results highlighted the cardio-protective effect of tanshinone IIA on MI/RI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition and the modulation of Th17/Treg cells differentiation.

Regulation Effect of Myeloid Leukemia No.1 Chinese Herb Medicine Prescription Combined with Chemotherapy on Th17 Cells in Bone Marrow of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the regulation effect of myeloid leukemia No.1 Chinese herb medicine prescription combined with chemotherapy on Th17 cells in bone marrow fluid of AML patients, so as to provide guidance for improving AML treatment effect and patients' long-term survival.@*METHODS@#Seventy patients with AML who were hospitalized in Department of Hematology, Wuwei People's Hospital from April 2017 to August 2019 were selected and enrolled in AML group, 25 healthy volunteers were selected and enrolled in control group; then according to therapeutic regimen, AML patients were divided into 2 groups: combined therapy group (myeloid leukemia NO.1 Chinese herb medicine prescription combined with chemotherapy) and non-combined therapy group (chemotherapy alone). Flow cytometry was used to detect the ratio of CD3@*RESULTS@#The ratio of CD3@*CONCLUSION@#Th17 cells expression in bone marrow of newly diagnoses and relapsed AML patients significantly increase, and decrease significantly after treatment. Myeloid leukemia No.1 Chinese herb prescription combined with chemotherapy can significantly increase the CR rate and reduce the RL rate for AML.

Significance of Tim-3 in The Imbalance of Th17/Treg in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the singnificance of Tim-3 in Th17/Treg balance in patients with multiple myeloma (MM).@*METHODS@#Fifty-six newly diagnosed MM patients and 30 healthy people were enrolled. Flow cytometry was used to detect the expression of Tim-3 on CD4@*RESULTS@#Compared with the control group, the expression of Tim-3 on CD4@*CONCLUSION@#The ratios of Th17/Treg, IL-17/IL-10 and Tim-3

Immune mechanisms involved in the coexistence of oral lichen planus and autoimmune thyroid diseases / 浙江大学学报·医学版

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease with unclear etiology. Autoimmune thyroid diseases (AITD) is a type of autoimmune disease characterized by increased thyroid-specific antibodies. In recent years, more and more studies have found that the incidence of AITD is increased in OLP patients. The occurrence and development of OLP and AITD may be related to the expression of thyroid autoantigen in oral keratinocytes, the imbalance of thyroid hormone （Th）1/Th2 and Th17/Treg cell subsets, the abnormal quantity and function of follicular helper T cells and chemokines and the specific killing ability of CD8 T cells to target cells. In this article, the possible immune mechanisms involved in the coexistence of OLP and AITD are reviewed to provide insights for the diagnosis, treatment and prevention of these two diseases from the perspective of immunology.

Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium / 国际口腔科学杂志·英文版

Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.

Effect and Mechanism of Epimedium Polysaccharide on Bone Marrow Hematopoietic Function and Th17/Treg Balance in Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To observe the effects of Epimedium polysaccharides (EPS) on bone marrow hematopoietic function and Th17/Treg balance in aplastic anemia (AA) mice, and preliminarily explore its therapeutic mechanism.@*METHODS@#Forty BALB/C mice were randomly divided into control (control), model (model), stanozolol (stanozolol) and epimedium polysaccharide (EPS) group, with 10 mice in each group. Except for the control group, Acetophenazine, Gy irradiation and cyclophosphamide triple application were used to establish AA models for the other groups. After the model was established, the stanozolol group was intragastrically administered with 4 mg/kg stanozolol suspension, the EPS group was intragastrically administered with 100 mg/kg epimedium polysaccharide, while the control group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage once a day, for 14 consecutive days. The automatic animal blood analyzer was used to detect the changes in peripheral blood hemoglobin (Hb), red blood cells (RBC), white blood cells (WBC) and platelets (PLT), flow cytometry was used to detect the proportion of Treg and Th17 cells, the levels of interleukin 2 (IL-2), interleukin 11 (IL-11) and tumor necrosis factor α (TNF-α) were detected by ELISA, the number of nucleated bone marrow cells was counted, HE staining and immunohistochemical staining were used to detect the number, the proliferation and apoptosis of bone marrow cells, Western blot was used to detect the expression of signal transducer and activator of transcription 3 (STAT3), retinoic acid receptor-related orphan receptor γ (RORγt), transducer and activator of transcription 5 (STAT5) and fork head transcription factor 3 (Foxp3).@*RESULTS@#Compared with the model group, the levels of Hb, RBC, WBC and PLT in the peripheral blood of mice in stanozolol and EPS group significantly increased, the proportion of Th17 cells was significantly reduced, and the proportion of Treg cells significantly increased. The levels of IL-2 and TNF-α in serum were significantly reduced (P<0.05), the level of IL-11 significantly increased (P<0.05), the number of bone marrow nucleated cells significantly increased (P<0.05), the positive rate of Ki-67 significantly increased (P<0.05) and the positive rate of Caspase-3 was significantly reduced (P<0.05). At the same time, the protein expression of STAT3 and RORγt significantly decreased, and the protein expression of STAT5 and Foxp3 increased, the difference showed statistically significant (P<0.05).@*CONCLUSION@#EPS can promote the recovery of bone marrow hematopoietic function in AA mice and improve Th17/Treg imbalance, the mechanism may be related to the inhibition of STAT3/RORγt expression and promotion of STAT5/Foxp3 expression.

Effect of type 2 diabetes mellitus on mandibular bone regeneration and the expression of T helper cell 17/regulat-ory T cell-related factors in mice / 华西口腔医学杂志

OBJECTIVES@#To observe the effect of type 2 diabetes mellitus (T2DM) on mandibular bone regeneration and the expression of factors related to T helper cell 17 (Th17 cell) and regulatory T cell (Treg cell) in mice.@*METHODS@#Thirty-six 6-week-old C57BL/6J male mice were randomly divided into normal control (NC) and T2DM groups. Fasting blood glucose levels were detected 0 d, 7 d, 14 d, and 28 d after surgery for mandibular defects. Hematoxylin-eosin (HE) staining was used in observing the bone after 7 d, 14 d, and 28 d of the healing process. Immunohistochemical staining was used in observing the expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), forkhead box protein P3 (Foxp3), retinoic acid related orphan receptor gamma T (RORγt), and protein tyrosine phosphatase non-receptor type 2 (PTPN2) after 7 d, 14 d, and 28 d of healing.@*RESULTS@#HE staining showed that the area with new bones in the T2DM group was significantly smaller than that in the NC group. Immunohistochemical staining showed that the expression of osteogenesis related proteins ALP and RUNX2 were significantly reduced in the T2DM group. In addition, the number of RORγt positive cells increased, whereas the number of Foxp3 positive cells and the expression PTPN2 decreased significantly in the mandibular bone defect in mice with T2DM.@*CONCLUSIONS@#T2DM significantly inhibit mandibular bone regeneration in mice. Decline in PTPN2 expression and the transition of Treg and Th17 may be the underlying molecular mechanisms.

Effect of different orthodontic forces on the expression of T helper cell 17 cell-related cytokines in the pressure side of periodontal tissue in rats / 华西口腔医学杂志

OBJECTIVES@#This study aimed to explore the changes in the expression of the characteristic transcription factor retinoid related orphan receptor γt (RORγt) and the cytokine interleukin-17 (IL-17) of T helper cell 17 (Th17) in the pressure side of the periodontal tissue of rats under different orthodontic forces. Their effects on the expression of osteoprotegerin (OPG) and the quantity of osteoclast (OC) were also explored. The role of Th17 cell in alveolar bone remodeling under different forces was preliminarily investigated.@*METHODS@#A total of 108 rats were chosen and randomly divided into three groups. Mesial forces of 0, 50, and 100 g were loaded on the maxillary first molar in the three groups. The rats were executed at 0, 1, 3, 5, 7, and 14 days. The expression of RORγt mRNA was quantified by real-time quantitative polymerase chain reaction. The expression of IL-17 protein was quantified by enzyme linked immunosorbent assay. The expression levels of RORγt and OPG proteins were quantified, and the quantity of OC was counted via immunohistochemistry.@*RESULTS@#The expression levels of RORγt and IL-17 and the quantity of OC increased first and then decreased in the 50 and 100 g groups, and the peak values of the two groups were on days 5 and 7, respectively. The expression levels in the 50 g group basically recovered to normal level on day 14, while that in the 100 g group remained at a high level. The expression levels in the 50 g group were higher than those in the 0 g group and lower than those in the 100 g group. The expression of OPG in the 50 g group decreased first, then increased, and finally decreased. It basically recovered to normal level on day 14. The expression of OPG in the 100 g group decreased first and then increased. It remained at a high level on day 14. The expression in the 50 g group was significantly higher than that in the 0 g group on day 7, while the expression in the 100 g group was significantly higher than that in the 0 g group on day 14.@*CONCLUSIONS@#RORγt, IL-17, and OPG were expressed regularly over time under different orthodontic forces, indicating that Th17 participated in the process of bone resorption on the pressure side of periodontal tissue by secreting IL-17.

Correlations between alterations of T-helper 17 cells and treatment efficacy after concurrent radiochemotherapy in locally advanced cervical cancer (stage IIB-IIIB): a 3-year prospective study / 中华医学杂志(英文版)

BACKGROUND@#Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy.@*METHODS@#A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB-IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8- interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-β (TGF-β), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS).@*RESULTS@#We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-β levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-β level significantly decreased compared with the levels before cCRT (P < 0.05).@*CONCLUSION@#Circulating Th17 cells in the LACC patients (FIGO stage IIB-IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.

Transcriptomics study of coronary slow flow disease and verification of differentially expressed genes / 中华心血管病杂志

Objective: To determine the differentially expressed genes between patients with coronary slow flow (SCF) and healthy controls, as well as to define the signal pathways and protein interactions related to the pathogenesis of the disease. Methods: A total of 43 hospitalized SCF patients in the year of 2018 and 43 healthy subjects, who underwent health checkup in the same year, were enrolled in this study. General data were obtained, blood samples were collected to determine the related indicators of glucose metabolism, lipid metabolism and kidney metabolism. RNA was extracted from blood monocytes, and the differential gene expression profiles were investigated by RNA-Seq. GO function annotation, KEGG pathway enrichment, protein interaction network analysis (PPI) and phenotype analysis were performed. The levels of related cytokines were detected by ELISA, and qPCR was used to verify differentially expressed genes of the two groups. Results: In the SCF group, there were 27 (62.79%) males and 16 females (37.21%), the average age was (54.3±8.8) years. In the control group, there were 29 males (67.44%) and 14 females (31.56%), the average age was (57.2±8.3) years. The percent of smoking history, abnormal fasting blood glucose, abnormal blood lipid levels and body mass index were significantly higher in the SCF group than in the control group (all P<0.01). There were 117 differentially expressed genes between SCF patients and healthy controls, of which 73 were up-regulated and 44 were down-regulated. Biological function analysis of the differentially expressed genes showed that these genes were mainly related to antigen processing and presentation, cell phagocytosis, immunoglobulin, intestinal immune network, Th1 and Th2 cell differentiation and Th17 cell differentiation pathways. The expression levels of inflammatory cytokines IL-6, IL-10, tumor necrosis factor-α and interferon-γ were significantly higher in SCF patients than in healthy controls (all P<0.05). Among the top 12 genes with the most significant differences between the two groups, qPCR analysis indicated consistent results with the transcriptome results in 11 out of 12 genes. PPI analysis showed that FPR2 and THBS3 proteins were at the core of the entire protein interaction network. Conclusion: Genes such as FPR2 and THBS3 may play important roles in the pathogenesis of SCF through immune-related pathways such as antigen processing and presentation and Th17 cell differentiation.

Dramatic secukinumab-mediated improvements in refractory leprosy-related neuritis via the modulation of T helper 1 (Th1) and T helper 17 (Th17) immune pathways

Abstract A 39-year-old woman was diagnosed with relapsed multibacillary leprosy and refractory neuritis. Here, we describe an evident loss of therapeutic effectiveness after the third pulse of corticosteroids, which may be attributed to tachyphylaxis and the posterior modulation of interferon- γ (IFN-γ), tumor necrosis factor- α (TNF-α,) interleukin-17A (IL-17A), and IL-12/23p40 after the induction phase of secukinumab. In this case, plasma cytokine analysis showed that secukinumab induced a reduction in IL-17 concomitant with impressive clinical improvements in the patient's neural function. Interestingly, secukinumab induced reductions in cytokines related to Th1 responses and earlier stages of the Th17 response, including IL-23/12.

Innate and Th1/Th17 adaptive immunity in acute and convalescent Brazilian borreliosis disease

ABSTRACT Introduction: Brazilian borreliosis (BB) disease is an infectious disease transmitted by ticks that mimics Lyme disease (LD) from the Northern Hemisphere. The BB clinical picture is characterized by a pathognomonic skin lesion (migratory erythema) and joint, neurological, cardiac and psychiatric symptoms. Innate and Th1/Th17 adaptive immunity seem to play an important role in the pathogenesis of Lyme disease. Objective: The aim of this study was to characterize the role of innate and Th1/Th17 adaptive immunity in BB patients with acute (<3 months) and convalescent (>3 months) disease. Methods: Fifty BB patients (28 with acute and 22 with convalescent disease) without treatment and 30 healthy subjects were evaluated. Levels of 20 cytokines or chemokines associated with innate and Th1/Th17 adaptive immunity were analyzed using Luminex (Millipore Corp., Billerica, MA). Results: Overall, BB patients had increased levels of IL-8 (6.29 vs 2.12 p = 0.002) and MIP-1α/CCL3 (5.20 vs 2.06, p = 0.030), associated with innate immunity, and MIP3B/CCL19 (Th1; 297.86 vs 212.41, p = 0.031) and IL-17A (Th17; 3.11 vs 2.20, p = 0.037), associated with adaptive immunity, compared with the levels of healthy controls. When comparing acute BB vs. convalescent BB subjects vs. healthy controls, IL-1β, IL-8 and MIP-1α/CCL3 (innate mediators) levels were highest in patients in the acute phase of disease (p < 0.05). TNF-α was associated with disseminated symptoms and with humoral reactivity against Borrelia burgdorferi. IL-10 was significantly correlated with IL-6 (r = 0.59, p = 0.003), IL-8 (r = 0.51, p < 0.001), MIP-1α/CCL3 (r = 0.42, p < 0.001) and MIP-3β/CCL19 (r = 0.40, p = 0.002) in all BB patients. Conclusions: This is the first study describing that innate and Th1/Th17 adaptive immunity play a crucial role in BB disease. Furthermore, innate mediators are particularly important in acute BB disease, and TNF-α is associated with evolution of BB symptoms.

Perfil de citocinas Th1, Th2, Th17 y otras citocinas pro inflamatorias (IL-1ß, IL-6 y TNFα) en el plasma de pacientes con cáncer gástrico / Th1, Th2, Th17 cytokine profile and other pro-inflammatory cytokines (IL-1ß, IL-6 and TNFα) in the plasma of patients with gastric cancer

El cáncer gástrico (CG) es la neoplasia del tubo digestivo más prevalente en el mundo, asociada a factores genéticos del hospedero y externos, como infección por Helicobacter pylori. La patogénesis incluye inflamación crónica mediada por citocinas del microambiente tumoral, detectables sistémicamente. Estudios previos reportan niveles séricos de citocinas y su contribución al diagnóstico de CG. El presente estudio analiza el perfil de citocinas del tipo de Th1(IFNγ), Th2(IL-4 e IL-10), Th17(Th-17A) y otras pro inflamatorias: IL-1ß, IL-6 y TNF-α, en plasma de 70 casos de pacientes con CG comparándolos con 132 sujetos sanos equiparables en edad y sexo. Los casos provinieron del Hospital Roosevelt e Instituto Nacional de Cancerología de Guatemala (Incan) y formaron parte de un estudio previo. Se analizó la base de datos clínicos, patológicos y epidemiológicos. Se midieron los niveles de citocinas utilizando el sistema "MSD MULTI-SPOT Assay System". La edad promedio de los casos fue 59.5 años, (DE 13.0), 51%, eran positivos para IgG anti H. pylori. Un 71% presentó adenocarcinoma grado III (Borrman), según clasificación de Lauren 55% tenían tipo intestinal. Las siete citocinas cuantificadas se encontraron significativamente elevadas (p < .05) en el plasma de los casos respecto a sus controles. Los casos de CG tipo difuso presentaron niveles de IFNγ significativa-mente elevados. Por regresión logística, las citocinas IL-6 e IL-10, están asociadas significativamente a CG (p < .05) independientemente del estatus de infección por H. pylori. Se destacan la IL-6 e IL-10 como las principales citocinas asociadas a la presencia de CG.

Gastric cancer (GC) is the most prevalent gastrointestinal neoplasm in the world, associated with host and external genetic factors, such as Helicobacter pylori infection. The pathogenesis includes chronic inflammation mediated by cytokines of the tumor microenvironment, systemically detectable. Previous studies report serum levels of cyto-kines and their contribution to the diagnosis of GC. The present study analyzes the profile of cytokines of the type Th1 (IFNγ), Th2 (IL-4 and IL-10), Th17 (Th-17A) and other pro-inflammatory: IL-1ß, IL-6 and TNF-α, in plasma of 70 cases of patients with GC compared with 132 healthy subjects comparable in age and sex. The cases came from the Roosevelt Hospital and the National Cancer Institute of Guatemala -Incan- and were part of a previous study. The clinical, pathological and epidemiological databases were analyzed. Cytokine levels were measured using the "MSD MULTI-SPOT Assay System". The average age of the cases was 59.5 years, (SD 13.0), 51% were positive for IgG anti H. pylori, 71% had grade III adenocarcinoma (Borrman), according to Laurenís classification, 55% had intestinal type. The seven cytokines quantified were found to be significantly elevated (p < .05) in the plasma of the cases compared to their controls. The diffuse GC cases presented significantly elevated IFNγ levels. By logistic regression, the cytokines IL-6 and IL-10 are significantly associated with GC (p < .05) regardless of the H. pylori infection status. IL-6 and IL-10 stand out as the main cytokines associated with the presence of GC.