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The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.
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Humans , Prognosis , Adenocarcinoma of Lung/genetics , Lung Neoplasms/genetics , Biological Assay , Cell CycleABSTRACT
ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ2=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ2=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ2=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4+， and CD4+/CD8+ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19-， HLA/DR+， and CD25+ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4+， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.
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Objective The concentrations of Th1/Th2/Th17 cytokines were compared in acute and chronic patients with brucellosis in order to understand the immune characteristics of acute and chronic brucellosis. Methods Using forward-looking design, 35 acute and 35 chronic patients with brucellosis were selected before treatment from the Endemic Disease Prevention and Control Center of Wulanchabu City as the research subjects with 25 local healthy persons as the healthy control group from March to June 2018. Enzyme linked immunosorbent assay (ELISA) method was used to determine the serum levels of Th1 cell cytokines interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), and interleukin-12 (IL-12); Th2 cell cytokines interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10);and Th17 cell cytokines interleukin-17 (IL-17). Results There were totally 25 patients in the control group, aged (46.48 ± 9.74) years, 15 males and 10 females;35 patients with acute brucellosis, aged(54.00 ± 7.65) years, 23 males and 12 females; and 35 patients with chronic brucellosis, aged (49.04 ± 8.24) years, 22 males and 13 females. The means of IFN-γ[(280.50 ± 40.48), (462.79 ± 47.94), (431.91 ± 40.39) ng/L], TNF-α[(292.17 ± 31.45), (481.21 ± 43.14), (433.70 ± 41.23) ng/L], IL-12 [(45.13 ± 5.55), (70.74 ± 7.58), (62.56 ± 5.73) ng/L], IL-4 [(383.24 ± 53.98), (606.11 ± 51.86), (550.66 ± 51.56) ng/L], IL-6 [(14.48 ± 2.17), (23.54 ± 2.39), (21.89 ± 2.26) ng/L], IL-10 [(140.48 ± 110.97), (464.49 ± 52.10), (404.73 ± 52.10) ng/L], and IL-17 [(13.71 ± 1.58), (23.79 ± 2.15), (21.37 ± 2.26) ng/L] were significantly different between control group, acute brucellosis group and chronic brucellosis group (F = 126.13, 152.58, 106.81, 139.28, 113.80, 155.86, 152.91, P < 0.05). Compared to control group, the levels of the seven cytokines in acute brucellosis and chronic brucellosis groups were significantly increased before treatment (P < 0.05). The levels of all of the seven cytokines in acute brucellosis group were significantly increased compared to chronic brucellosis group before treatment (P < 0.05). Conclusions There is a difference in the expression of Th1/Th2/Th17 cytokines in patients with acute and chronic brucellosis group. In the acute brucellosis group, the cell immunity induced by Th1 cells and the humoral immunity guided by Th2 cells are stronger than those in chronic brucellosis group.
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Objective :To study the effect of glucose on mouse CD4+ T cell differentiation. Methods :Mouse naïve CD4+ T cells cultured in the regulatory T cell (Treg), Th1, Th17 or Th2 differention condition were treated with different concentrations of glucose for 5 days. Treg, Th1, Th17 or Th2 percentages were measured by flow cytometry. Quantitative real-time PCR was used to detect the gene expressions of related cytokines and transcriptional factors. Results :The proportions of Treg and Th2 as well as the gene expressions of transforming growth factor-β, interleukin-4 (IL-4) and IL-13, and transcriptional factors, Foxp3 (forkhead box P3) and Gata3 (GATA binding protein 3), were increased significantly with the treatment of increasing concentration of glucose. On the contrary, with the glucose treatment, the percentages of Th1 and Th17 were reduced, and the gene expressions of the related cytokines and cytokine receptors, such as interferon-γ, IL-17A, IL-17F, IL-22 and IL-23R, and the related transcriptional factors, Tbx21 (T-box transcription factor 21) and RORC (RAR related orphan receptor C), were decreased consistently. Conclusion :Glucose promotes Treg and Th2 differentiation while inhibits Th1 and Th17 differentiation in vitro.
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Objective@#To investigate the inhibitory effects and mechanism of Triticum aestivum (TA) on anaphylaxis in ovalbumin (OVA)-sensitized mice.@*Methods@#Twenty-five female BALB/c mice were randomly divided into five groups (n=5), including control group, OVA group, 100 mg/kg TA group, 200 mg/kg TA group and DEX (dexamethasone) group. OVA (20 μg) and aluminum hydroxide (1 mg) were dissolved in 100 μl of PBS solution and injected into the abdominal cavity of each experimental mouse, while the mice in the control group were injected with 100 μl of 0.9% normal saline. All mice were given drinking water. The above processes were repeated two weeks later, and different concentrations of experimental drugs were diluted in 1% CMC (carboxymethyl cellulose) solution to feed mice. Allergic symptoms and behaviors of each mouse were scored in the process of feeding. On the 12th day after first sensitization, mice in the control and experimental groups were subcutaneously injected in the auricle with 20 μl of 0.9% saline solution and OVA, respectively. The thickness of each mouse′s auricle was measured 6 and 24 hours later. Histopathologic changes in auricle tissues were observed by hematoxylin-eosin(HE) staining 24 hours later. The mice were euthanized by cervical dislocation in the 6th week after first sensitization. Abdominal aorta serum samples were collected and tested for specific inflammatory cytokines (IgE, IgG1, TNF-α, IL-4) and anti-OVA antibodies (IgE, IgG1) by ELISA. ELISA and RT-PCR were used to detect the expression of IFN-γ, IL-4, IL-5, IL-12 and IL-13 after spleen lymphocytes were stimulated with different concentrations of drugs.@*Results@#Both the score of allergic symptoms and behavior and the thickness of the auricle of the OVA group were the highest among all groups (P<0.05). A TA dose-dependent decrease was found in both of the two parameters, which was confirmed by histopathological analysis. ELISA results showed that the plasma levels of IgE, IgG1, IL-4 and TNF-α in the experimental groups were significantly higher than those in the control group, but all of them were decreased in a TA dose-dependent manner. TA at the high concentration of 200 mg/kg was similar to DEX in inhibiting the expression of IgE and TNF-α. RT-PCR results showed that Th1 cytokines (IFN-y and IL-12) in the experimental groups increased significantly as compared with those in the control group (P<0.05). Expression of IFN-y and IL-12 was not significantly affected by TA at various concentrations, but markedly inhibited by DEX. The levels of Th2 cytokines (IL-4, IL-5 and IL-13) in the experiment groups were significantly higher than those in the control group (P<0.05). Compared with the OVA group, the levels of IL-4, IL-5 and IL-13 were significantly reduced in TA groups, especially in the TA 100 μg/ml group in which the expression of the three cytokines was decreased by about 60%, 18% and 20%, respectively.@*Conclusion@#TA helps to maintain immune balance by selectively inhibiting the expression of Th2 cytokines (IL-4, IL-5, IL-13), IgE and IgG and not influencing Th1 cytokines (IFN-γ and IL-12). It has an anti-allergic effect as it effectively suppresses allergic responses. This research provides both theoretical and experimental basis for further development of novel anti-anaphylactic treatment with TA.
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Objective To investigate the effect of doxycycline on the Th1/Th2 cell balance in experimental allergic encepha-lomyelitis(EAE)rats.Methods Forty female Wistar rats were randomly divided into the EAE control group,low,medium and high does DOX treatment groups,10 cases in each group.The onset situation in rats was observed.The IL-4 and IFN-γlevels secreted by peripheral blood mononuclear cells (PBMC)at the peak stage were detected.The levels of IL-1β,IL-10,TNF-αin brain tissue,and the albumin content in cerebrospinal fluid and serum were detected.The QA value was calculated.Results In each DOX group,the clinical symptoms of rats were alleviated compared with the EAE control group.In each DOX group,the PBMC secreting IFN-γlev-el and IFN-γ/IL-4 ratio in the onset peak stage were lower than those in the EAE control group,while the IL-4 level was higher than that in the EAE control group(P 0.05),but the difference between other DOX groups had statistical significance(P <0.01).The IL-1βand TNF-αlevels of brain tissue and QA value during onset peak stage in various doses DOX groups were decreased compared with the EAE control group,while the IL-10 level was increased compared with the EAE control group(P <0.05).With the DOX dose increasing,the levels of IL-1β,TNF-αand QA value in various doses DOX groups became lower,the IL-10 level became high-er,there was statistically significant difference among various doses DOX groups (P <0.05 ).Conclusion DOX can obviously alle-viate the clinical symptoms of EAE rats,its mechanism may be related with that DOX could decrease the level of Th1 cytokine and increase the level of Th2 cytokine,correct the Th1/Th2 cell balance,thus protect the blood brain barrier(BBB).
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Th2 cell immunity is required for host defense against helminths, but it is detrimental in allergic diseases in humans. Unlike Th1 cell and Th17 cell subsets, the mechanism by which dendritic cells modulate Th2 cell responses has been obscure, in part because of the inability of dendritic cells to provide IL-4, which is indispensable for Th2 cell lineage commitment. In this regard, immune cells other than dendritic cells, such as basophils and innate lymphoid cells, have been suggested as Th2 cell inducers. More recently, multiple independent researchers have shown that specialized subsets of dendritic cells mediate Th2 cell responses. This review will discuss the current understanding related to the regulation of Th2 cell responses by dendritic cells and other immune cells.
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Humans , Basophils , Dendritic Cells , Helminths , Interleukin-4 , Lymphocytes , Th1 Cells , Th17 Cells , Th2 CellsABSTRACT
PURPOSE: Chitin is a potent adjuvant in the development of immune response to inhaled allergens in the airways. According to other studies, chitin is known as multi-faced adjuvants which can induce Th2 responses. Recently, we found that TNF-α is a key mediator in the development of Th2 cell response to inhaled allergens. Here, we evaluated the immunologic mechanisms in the development of airway hypersensitivity to inhaled allergens, enhanced by house dust mite (HDM)-derived chitin. METHODS: The role of TNF-α and TLRs was evaluated in an airway hypersensitivity mouse model induced by a sensitization with an allergen (ovalbumin, OVA) and HDM-derived chitin using mice with the null mutation of target genes. RESULTS: The present study showed that airway sensitization with HDM-derived chitin plus OVA enhanced OVA-induced airway inflammation v. OVA alone. This phenotype was associated with the increased expression of Th1, Th2, and Th17 cytokines and also with the enhanced production of OVA-specific IgE, IgG1, and IgG2a. As for T cell responses, OVA-specific Th2 cell response, enhanced by chitin, was abolished by the treatment of chitinase, whereas Th1 and Th17 cell responses enhanced by this treatment. Moreover, the null mutation of the TNF-α gene revealed similar effects as the chitinase treatment. In contrast, all the OVA-specific T cell responses, enhanced by chitin, were blocked by the absence of TLR2, but not of TLR1, TLR4, or TLR6. CONCLUSIONS: In conclusion, these data suggest that HDM-derived chitin may enhance airway hypersensitivity to inhaled allergens, via the TLR2-dependent pathway, and that chitin-induced TNF-α can be a key mediator in the development of Th2 cell response to inhaled allergens.
Subject(s)
Animals , Mice , Allergens , Chitin , Chitinases , Cytokines , Dust , Hypersensitivity , Immunoglobulin E , Immunoglobulin G , Inflammation , Ovum , Phenotype , Pyroglyphidae , Th17 Cells , Th2 CellsABSTRACT
Asthma is severely harmful to the health of the children with respiratory tract infection,but its etiology and pathogenesis is not yet entirely clear.Currently,it is considered that Th1/Th2 cell function imbalance is the immunological basis.Regulatory T cells (regulatory T cell,Treg) is one of the hot spots in recent years,regulating the immune system negatively.The decrease in the number of cells leads to immune suppression dysfunction,and creats the conditions for the development of the disease for asthma.Recent studies have found that Treg cells play an important role in the regulation of Th2 cell activation,which not only completes the traditional theories of Th1/Th2,but also provides a new method for preventing and controlling asthma by clinical use of Treg cells.
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Background Mooren 's ulcer is an immune-related corneal inflammatory disease,and its pathogenesis remains below understood.Previous studies showed that the imbalance of T helper cell type 1 (Th1) and Th2 cell play important roles in the development of some autoimmune diseases.Thereby the influence of Th1/Th2 cells on the pathogenesis of Mooren's ulcer is being concerned.Objective This study was to investigate the change of Th1 and Th2 subsets in periphery blood of patients with active Mooren's ulcer.Methods Eleven consecutive patients with active Mooren's ulcer and 8 age-and gener-matched healthy controls were included in Zhongshan Ophthalmic Center,Sun Yat-sen University from January 2012 to July 2013 under the approval of Ethic Committee of this hospital and informed consent of each subject.The peripheral blood samples of all the subjects were obtained separately and periphery blood mononuclear cells (PBMCs)were isolated.The percentages of Th1 and Th2 in the PBMCs were assayed by flow cytometer.The relative expressions of T-bet mRNA,GATA-3 mRNA and signal transducer and activator of transcription 5 (Stat5) mRNA in the PBMCs were examined and compared by real-time fluorescence quantitative PCR (RT-qPCR) Results The percentage of Th1 cells in CD4+ T cells and Th1/Th2 value was 0.21％ (0.11％,0.31％) and 8.01 (4.49,12.01) respectively in the Mooren's ulcer group,which were significantly lower than 0.35％ (0.22％,0.71％)and 23.90 (22.49,33.49)in the normal control group,respectively (Z =-2.01,P =0.04 ; Z =-3.06,P =0.00).However,no significant difference was found in the percentage of Th2 between the two groups (Z=-1.98,P＞0.05).The relative expressions of T-bet mRNA and GATA-3 mRNA in PBMCs were significantly lower in the Mooren's ulcer group than those in the normal control group (Z =-3.47,-3.06,both at P=0.00) ;While the relative expression of Stat5 mRNA in PBMCs was insignificant changed between the two groups (Z =-1.05,P =0.33).Conclusions Th1 and Th2 cells are unbalanced in the active Mooren's ulcer patients.In addition,the down-expression of relevant transcription factors in peripheral blood also is seen in these patients.It is inferred that Th1 and Th2 cells may participate in the progress of Mooren's ulcer.
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Acupuncture could modulate the immune responses and is clinically used for the treatment of some allergicand immunological disorders. But the benefits of the clinical use of acupuncture for the treatment of theimmunoligical diseases have not been fully established. Further, the mechanisms by which acupuncture affects the immune responses have not been clarified. Here, we review the reports about the clinical effects of acupuncture on immunological diseases and about the basic mechanisms of immune modulation by the acupuncture. From these reports and our experimental data, acupuncture could influence the amount of cytokines produced by immunocompetent cells, so we present the hypothetical mechanisms of immunoregulatory action of acupuncture.
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Objective To explore the immuniated function of infants with bronchiolitis. Methods In vitro production of IL-18,12, 10, 4, IFN-? by peripheral blood mononuclear cells (PBMC) and plasma IgE of bronchiolitis infants measured by enzyme-linked im-munosorbent assay, expression of lymphocyte activation gene - 3 (LAG - 3) mRNA from PBMC measured by semi - quantitative RT- PCR.Forteen healthy children were as normal control. Results Compared with normal control, IL - 12 (390. 94 ? 95. 88 vs 452.44?195.07) ng/L and IL-18(146.23? 55. 81 vs 246.69?121.29) ng/L activity were significantly decreased (P0.05) ;The levels of IL-4(30. 52 ? 17. 65 vs 16.20? 8.94) ng/L and IL-10 (302. 40 ? 100.04 vs 195.30? 84.01) ng/L were elevated significantly(P
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Objective To investigate the TH1/TH2 patterns by calculating the percentage of TH1, TH2 cells, and the TH1/TH2 ratio of peripheral blood from patients with pregnancy-induced hypertension (PIH). Methods The percentage of TH1 and TH2 cells in peripheral blood from 15 normal pregnant controls and 20 PIH patients (including 12 moderate and 8 severe cases) were calculated using flow cytometry for the analysis of both the surface marker CD3 CD8 and intracellular cytokines, interleukin-4 (IL-4), and interferon-? (IFN-?). Results The percentage of TH1 cells and the ratio of TH1/TH2 in PIH patients were significantly higher than those in the normal third-trimester pregnant controls [(20.50?4.02)% vs (12.57?2.18)%, P
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Objective To analyze the relationship between serum Th1/Th2 cytokines levels and autoantibodies against thyroid, and explore the role of Th1/Th2 cellular immunity imbalance in the pathogenesis of autoimmune thyroid diseases(AITD). Methods 21 patients with Graves'desease(GD), 18 cases with Hashimoto's thyroiditis(HT), 17 cases with non-toxic nodular goiter(NTNG) and 20 healthy subjects were enrolled in this study. The serum concentrations of their Th1 cytokines (IFN-?,IL-2) and Th2 cytokines (IL-4,IL-10) were assayed by ELISA. The serum levels of their thyrotropin receptor antibodies(TRAb), thyroglobulin antibodies (TGAb) and thyroid peroxidase antibodies(TPOAb) were measured by routine methods. The relationship between the serum Th1, Th2 cytokines levels and serum TRAb, TGAb, TPOAb levels were analyzed. Results The serum levels of IL-4 and IL-10 in patients with GD were significantly higher than those in patients with HT,NTNG and healthy subjects(P
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T cell mediated immunity amlifies macrophage capacities to kill and digest the bacilli through production of interferon-gamma (IFN-gamma). The secreted cytokines of Th1 and Th2 cells can mutually regulate and inhibit each other's function. Therefore, the fine balance between the secreted cytokines is important for the resulting nature of tuberculosis. In this study, activation marker and cytokine production profiles were compared in patients with active tuberculosis and healthy control, and according to degree of radiographic extent and pleural involvement. METHOD:Forty-four patients with active pulmonary tuberculosis and 25 normal controls were recruited. We measuerd soluble interleukin-2 receptor(sIL-2R), IFN-r, IL-4 and IL-5 produced from blood mononuclear cells in vitro stimulation with phytohemagglutinin by ELISA. RESULTS: The sIL-2R and IFN-gamma from patients with active pulmonary tuberculosis were significantly lower than normal control, while IL-4 and IL-5 were not different between two group. The sIL-2R and IFN-r decreased in proportion to the extent of pulmonary involvement, and the sIL-2R and IFN-r from pulmonary tuberculosis with pleural effusion were significantly lower than those without pleural effusion. CONCLUSION: At the level of systemic T cells, development of tuberculosis is associated with diminished Th1 but not enhanced Th2 response.
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Humans , Cytokines , Enzyme-Linked Immunosorbent Assay , Immunity, Cellular , Interferon-gamma , Interleukin-2 , Interleukin-4 , Interleukin-5 , Macrophages , Pleural Effusion , T-Lymphocytes , Th2 Cells , Tuberculosis , Tuberculosis, PulmonaryABSTRACT
Objective To investigate the Th1/Th2 cells imbalance in childhood primary nephrotic syndrome(PNS)and its relation to disease activity. Methods Percentage of T-helper-1(Th1) and T-helper-2 (Th2) cells was examined by three-color flow-cytometry in 21 cases of first-onset PNS, 16 cases of remission PNS and 10 healthy children. Results The percentage of Th1, Th2 and Th0 cells in healthy children was (13. 42?4. 36)% , (2. 53 ? 1. 97)% and (1. 25?0. 92)% respectively. In the patients with first-onset PNS, the percentage of Th1, Th2 and Th0 cells was significantly decreased as compared to healthy children [(2. 34 ?2. 09)%, (1.02?0.96)% and (0.40?0.38)% respectively, all P 0. 05]. Because of relatively low percentage of Th1 cells in contrast to Th2 cells in the patients with first-onset PNS, Th1/Th2 ratio was also significantly reduced in those patients, as compared to the patients with remission PNS and the healthy children (2. 43 ? 2.65 vs 4. 17?2. 32 and 5. 41?2. 77, both P
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Objective:To investigate the influences of laparoscopic surgery on Th1/Th2 balance in patients with uterine myomas.Methods:In a prospective study,the number of the Th subsets,Th1/Th2 ratio,the serum level of IL-18 and IL-10 in 20 patients submitted to laparoscopic operation and 20 patients undergoing conventional open operation were evaluated preoperatively as well as 2,24,48 h postoperatively.Results:The level of Th1 cell,IL-18,and the Th1/Th2 ratio decreased significantly (laparoscopic group: P