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Th17 cell is a newly developed CD4 +T cell subsets,play a pro-inflammatory role and participate in the pathogenesis of many autoimmune diseases mainly through secretion of cytokines such as interleukin-17 (IL-17),many of the biological effects of Th17 cells are closely related to the IL-17,this article reviews the relation-ship between Th17/IL-17 axis and related cytokines and kidney the pathogenesis of disease,in order to more in-depth understanding of the pathogenesis of kidney disease,provide the basis for looking for new targets of diagnosis and treatment of kidney disease and new treatment strategies.
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Objective To test whether T helper 17 (Th17) cells was involved in the pathogenesis of multiple sclerosis (MS) by conducting a meta-analysis of the researches documenting the levels of Th17 cells and Th17-related cytokines [interleukin (IL)-17,IL-23] in patients with MS.Methods We identified articles reporting proportion of Th17 cells and the serum levels of IL-17,IL-23 in MS patients by searching CNKI,Wanfang med online,Embase,PubMed,Cochrane,WebofKnowledge,Food and Drug Administration (FDA).gov,and ClinicalTrials.gov.We registered this study at the International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42017059113).The evidence level of selected studies was identified by guidelines from the Oxford Center for Evidence-Based Medicine 2011.We employed the Newcastle-Ottawa Quality Assessment Scale (Case Control Studies) to perform the included resear.Stata 12.0 was adopted for processing Meta-analysis of the data by using a random effects model.Results A total 16 researches were included in our Meta-analysis from 587 identified studies.The proportion of Th17 cells [1.89％(1.10％,2.69％),P＜0.01] and the levels of serum IL-17 [2.77(1.77,3.77) pg/ml,P＜0.01] and IL-23 [2.96(1.51,4.40)pg/ml,P＜0.01] increased dramatically in MS individuals compared with control subjects.Conclusion The results of this Meta-analysis has demonstrated that MS patients have a higher proportion of Th 17 cells in higher levels of serum IL-17 and IL-23 compared to control subjects,which has demonstrated that Th17 cells may play an vital role in the pathogenesis process of MS patients.
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AIM:To explore the effect of Delta-like ligand 4 (Dll4)-Notch signaling pathway blockade on the development of Thelper 17(Th17) cells in the asthmatic mice.METHODS:Male BALB/c mice were randomly divided into 5 groups:control group, asthma group, normal saline group, anti-Dll4 antibody group, and immunoglobulin G group.The protein expression of Dll4 was detected by immunohistochemical staining.The proportion of Th17 cells in mouse spleen isolated CD4+ T cells was measured by flow cytometry.The protein expression of Th17 transcription factor retinoid-related orphan receptor γt (RORγt) was determined by Western blot.The serum level of interleukin (IL)-17 was measured by enzyme-linked immunosorbent assay (ELISA).RESULTS:The expression of Dll4 in the lung tissues from asthma group significantly increased as compared with anti-Dll4 antibody group.The proportion of Th17 cells in CD4+ T cells was significantly down-regulated, and the protein expression of RORγt in the lung tissues was significantly reduced in anti-Dll4 antibody group compared with asthma group (P<0.05).Moreover, the serum level of IL-17 in anti-Dll4 antibody group was significantly reduced compared with asthma group (P<0.01).CONCLUSION:The blockade of Dll4-Notch signaling pathway inhibits the differentiation of Th17 cells in asthmatic mice.
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AIM: To investigate the immunomodulatory effect of pachyman polysaccharides (PPS) on T helper 17 cell (Th17)/regulatory T cell (Treg) balance in the peripheral blood of systemic lupus erythematosus (SLE) patients.METHODS: The CD4+ T cells were isolated from the peripheral blood samples obtained from 45 SLE patients and 35 healthy controls enrolled in our study using magnetic bead separation method.The proportions of Th17 and Treg cells were measured by flow cytometry.The CD4+ T cells from SLE patients and healthy controls were treated with PPS.The cytoto-xicity of PPS was evaluated by detecting cell viability with MTT assay.The contents of interleukin-17 (IL-17), IL-6, IL-10 and transforming growth factor-β (TGF-β) were measured by ELISA.The expression of retinoid-related orphan receptor γt (RORγt) and forkhead box protein P3 (Foxp3) at mRNA and protein levels was determined by RT-qPCR and Western blot, respectively.RESULTS: The Th17 cells were significantly elevated, while Treg cells were obviously decreased in the SLE patients compared with the healthy control group (P<0.05).Compare with control group, the contents of IL-17 and IL-6 were decreased, while the contents of IL-10 and TGF-β were increased (P<0.05).The expression of RORγt at mRNA and protein levels was down-regulated and the expression of Foxp3 was up-regulated (P<0.05).The ratio of Th17/Treg was decreased in 100 μg/L nontoxic PPS-treated CD4+ T cells isolated from the SLE patients (P<0.05).CONCLUSION: PPS treatment inhibits Th17 cells and elevates Treg cells in the CD4+ T cells isolated from SLE patients, which may have a therapeutic effect on SLE patients.
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Objective To explore the differences of Th17 population and serum transforming growth factor (TGF)-β1 levels between early-and late-stage primary biliary cirrhosis (PBC) and their roles in pathogenesis.Methods Peripheral Th17 counts were analyzed by flow cytometry.The expression of IL-17A in peripheral blood mononuclear cells and TGF-β1 were measured by real-time quantitative polymerase chain reaction.Serum concentration of TGF-β1 was measured by enzyme-linked immunosorbent assay.Liver biopsies were stained with hematoxylin-eosin to determine the pathological stage.Results were evaluated using KrustalWallis test followed by Mann-Whitney U tests for comparisons of Th17 population between patients with early and late PBC,patients with chronic hepatitis B (CHB) and health controls (HCs).ANOVA followed by LSD t-tests were used for comparing IL-17 mRNA,TGF-β1 mRNA and TGF-β1 serum concentration between groups.The correlations between Mayo risk score and peripheral Th17 of PBC patients,Mayo risk score and serum concentration of TGF-β1 was analyzed by Pearson correlation analysis separately.Results The peripheral Th17 population increased in patients with early PBC (1.03±0.33)％,compared to those with late PBC [(0.48± 0.13％,U=14.0,P＜0.01],CHB [(0.56±0.35)％,U=104.5,P＜0.01],and HCs [(0.36±0.17)％,U=8.0,P＜0.01],while TGF-β1 changed in the opposite direction.Serum concentration of TGF-β1 elevated in late PBC (43.0± 18.7) ng/ml compared with early PBC (29.5±12.2) ng/ml,t=2.85,P=0.006.Conclusion The opposite changes of Th17 population and TGF-β1 level in early and late PBC indicated their different roles in different stages.Th17 may contribute to the autoimmune response in early PBC,participate in the occurrence of autoimmune inflammation,while TGF-β1 to fibrogenesis in late stage.In addition,the possible regulation mechanisms of differentiation of Th17 by TGF-β1 cannot be ignored.
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Objective:To evaluate the roles of imbalance between peripheral blood T helper17(Th17) cells and CD4+CD25+regulatory T(Treg) cells in the pathogenesis of Anaphylactoid purpura(AP).Methods: Peripheral blood samples were obtained from fifty-two patients with AP and thirty age-and sex-matched healthy controls.The percentage of Th17 cells and Treg cells in peripheral blood were detected with Flow cytometry.Furthermore,the serum level of IL-6,IL-17,IL-22 and IL-23 and transforming growth factor (TGF)-βand IL-10 were detected with the use of enzyme linked immunosorbent assay(ELISA).Results: In comparison with the controls,the AP children showed a higher percentage of Th17 cells and an increased serum level of IL-6,IL-17,IL-22 and IL-23(P<0.05),but the percentage of Treg cells and the serum level of TGF-βand IL-10 were significantly lower in AP group(P<0.05).Con-clusion:AP children experience a change in the percentage of peripheral blood T helper17 cells and CD4+CD25+regulatory T cells in peripheral blood.The imbalance between the Th17 cells and Treg cells in peripheral blood may contribute to the development of Ana-phylactoid purpura.
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Objective To investigate the regulation of Sertoli cells on differentiation balance of allogeneic regulatory T cell (Treg)and T helper cell(Th17).Methods Sertoli cells ,bone marrow‐derived dendritic cells(DC) and T lymphocytes were iso‐latedandculturedinvitro.SertolicellsandDCcellswereco‐culturedwithallogeneicTcells,respectively.MorphologyofSertoli cells were verified under the light microscope and electron microscope. The expression of major histocompatibility complex (MHC)‐Ⅱ and B7‐H1 in Sertoli cells was detected by Western blot.Concentration of cytokines[transforming growth factor (TGF)‐β1 and IL‐17A etc. ] in supernatant was determined by enzyme linked immunosorbent assay(ELISA). The frequency of Treg cells differentiated from na?ve T cells was estimated by flow cytometry.Results Sertoli cells were successfully isolated and cultured in vitro.Western blot results showed the expression of MHC‐Ⅱ and B7‐H1 on Sertoli cells surface was increased significantly ,when Sertoli cells were co‐cultured with allogeneic na?ve CD4+ T cells(CD4+ CD62 L+CD25)in vitro.ELISA re‐sults showed the TGF‐β1 concentration in culture supernatant was significantly increased [from (174.89 ± 23.51) pg/mL to (823.10 ± 59.07) pg/mL ,P pressive cytokines derived from Sertoli cells can induce allogeneic na?ve T cells to differentiate into CD25+ Foxp3+ Treg cells in vitro.Sertoli cells can regulate the differentiation balance of allogeneic Treg/Th17 to induce the immune tolerance.
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Objective To investigate the nature of Th17 cells in murine cytomegalovirus(MCMV)infection during the acute stage,we characterized the frequency of IL-17A-producing CD4 T cells and the level of Th17 cytokines,IL-17A,in MCMV-infected mice.Methods BALB/c mice were randomly divided into two groups.One was infected with MCMV Smith for establishing disseminative infection; the other was sham-inoculated control.On day 3,7,14 and 28 of the experiment,three mice of each group were randomly chosen to be killed separately.Real-time PCR was used to detect MCMV loads in organs of MCMV-infected mice,the pathology of spleen was observed by HE staining.The frequency of CD4+IL-17A+ T cells in total splenocytes of mice was detected by flow cytometry.The level of IL-17A in culture supernatants of splenocytes was measured by double antibody sandwich ELISA.Results MCMV loads in salivary gland reached the peak on day 14 after MCMV infection,the most severe spleen injury was also shown on day 14,the frequencies of CD4+IL-17A+ T cells in total splenocytes increased significantly( all P＜0.01 ) in MCMV-infected mice than those in controls,and reached the peak on day 14 ( 1.14％ ±0.09％ vs 0.19％ ±0.04％,t =17.551,P=0.000).The levels of MCMV-specific IL-17A in culture supernatants were increased dramatically in MCMV-infected mice than those in controls on day 14 [ (81.98± 12.37) pg/ml vs (44.96±8.44)pg/ml,t=4.281,P=0.006].In MCMV-infected mice,correlation was positive between the levels of MCMV-specific IL-17A in culture supernatants and MCMV loads in salivary gland tissues (r=0.54,P＜0.05 ),the levels of IL-17 A in culture supernatants were higher in more severe spleen injury.Conclusion Thl7 cells and IL-17A were involved in the immunity response during acute MCMV infection.They may correlate with the persistence of MCMV and the pathology of spleen in infected mice.
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Objective To study the effects of pulse high volume hemofiltration (PHVHF) on the changes of Th17 cells (T helper 17 cells) and CD4 + CD25 + reguratory T cells (Treg cells) in peripheral blood of patients with sepsis and to evaluate the clinical value of this intervention. Methods The patients were included in this prospective study as per the criteria of sepsis set by America Chest Physicians College/America Society for Critic Care Medicine in 1992. The patients were excluded: ① immune system disorder, ② acute stroke, ③ myocardial infarction, ④ virus hepatitis,⑤ human immunodeficiency virus infection, ⑥ under immunosuppressive therapy. Forty patients (24 males, 16 females, aged from 25 to 75years) with sepsis in ICU were enrolled from January. 2008 to November. 2010. According to the severity of disease, the patients were divided into three groups; moderate sepsis group (n = 14, 8 males, 6 females) , severe sepsis group (n = 15, 9 males, 6 females) , and septic shock group (n = 11, 7 males, 4 females). The initially clinical data of three groups were comparable. Twenty healthy individuals served as controls. According to the mode of treatment, forty patients were also divided into two groups: conventional treatment group (group A, n= 15) in which patients were treated without PHVHF within 5 days after admission and trial group (group B, n=25) in which patients were treated with pulsed high volume hemofiltration (PHVHF) within 5 days after admission. In group B, high volume hemofiltration (70 mL · kg-1 · h-1) was given to patients for 6 ～ 8 hours, and then conventional continuous vein - vein hemofiltration (35 mL · kg-1 · h-1) for 16 ~ 18 hours. The total length of period for continuum blood scavenging was 24 hours as one cycle. The interval between two cycles of blood scavenging was 24 hours. The changes of Th17 cells and CD4+ CD25 + Treg cells of 40 patients were detected with flow cytometry on the 1st day and the 5th day after admission. The data were analyzed by using SPSS version 13. 0 software. Measurement data were analyzed with Paired-samples t-test, independent-samples t-test or one way ANOVA . Ratio of small samples was compared with fisher's exact test, and the correlation was analyzed by using Pearson correlation analysis. Results The rates of Th17 cells were( 0.91 ±0.38)%, (2.09 ±0. 53)% , (3.90 ±0. 80)% , and ( 1. 85 ±0.35)% in control, moderate sepsis, severe sepsis, and septic shock groups, respectively, while the rates of CD4+ CD25+ Treg cells were (0.39 ±0.23)%, (1. 72 ±0. 59)% , (2.72 ±0. 22)% , and (3. 55 ±0. 51)% , respectively. The rate of Thl7 cells on the 1st day was higher in severe sepsis group than that in other two groups ( P 0. 05). Moreover , the rate of CD4+ CD25 + Treg cells was up - regulated on the 1st day in the following order from high to low: septic shock group > severe sepsis group > sepsis group (P < 0.05). The rates of Th17 cells and CD4 + CD25 + Treg cells in patients of group B decreased in greater degree than that did in patients of group A (P < 0.05 ). Conclusions The changes of Th17 cells and CD4 + CD25 + Treg cells may play an important role in pathogenesis of sepsis, and the pulsed high volume hemofiltration may be one of the effective treatments for the patients with sepsis by regulating the rates of Thl7 cells and CD4 + CD25 + Treg cells.