CD4＋ helper T （TH） cells play crucial roles in immune responses. Recently a novel subset of TH cells, termed THIL-17, TH 17 or inflammatory TH （THi）, has been identified as critical mediators of tissue inflammati...CD4＋ helper T （TH） cells play crucial roles in immune responses. Recently a novel subset of TH cells, termed THIL-17, TH 17 or inflammatory TH （THi）, has been identified as critical mediators of tissue inflammation. These cells produce IL-17 （also called IL-17A） and IL-17F, two most homologous cytokines sharing similar regulations. Here we report that when overexpressed in 293T cells, IL-17 and IL-17F form not only homodimers but also heterodimers, which we name as IL-17A/F. Fully differentiated mouse THi cells also naturally secrete IL-17A/F as well as IL-17 and IL-17F homodimeric cytokines. Recombinant IL-17A/F protein exhibits intermediate levels of potency in inducing IL-6 and KC （CXCL 1） as compared to homodimeric cytokines. IL-17A/F regulation of IL-6 and KC expression is dependent on IL-17RA and TRAF6. Thus, IL-17A/F cytokine represents another mechanism whereby T cells regulate inflammatory responses and may serve as a novel target for treating various immune-mediated diseases.展开更多
类风湿性关节炎(rheumatoid arthritis,RA)是一种以慢性多关节滑膜炎为主要特征的自身免疫性疾病。虽然目前对于RA的确切发病机制尚不明确,但一般认为和T细胞相关。最近研究发现调节性T细胞(regulatory T cell,Treg)和Th17细胞在RA的发...类风湿性关节炎(rheumatoid arthritis,RA)是一种以慢性多关节滑膜炎为主要特征的自身免疫性疾病。虽然目前对于RA的确切发病机制尚不明确,但一般认为和T细胞相关。最近研究发现调节性T细胞(regulatory T cell,Treg)和Th17细胞在RA的发生发展中发挥重要作用。Th17细胞能够分泌促炎症因子IL-17,通过诱导基质金属蛋白酶(ma-trix metallo proteinases,MMPs)和破骨细胞生成,促进骨滑膜炎症、骨和关节损伤;而Treg则通过释放抑制性细胞因子IL-10和TGF-β发挥免疫效应,调控RA中的炎症性免疫应答过程。单独TGF-β作用下诱导初始T细胞分化为Treg,而在TGF-β和IL-6共同作用下诱导初始T细胞分化为Th17细胞,因此,Th17和Treg细胞在特定的细胞因子微环境下可以相互转化。调节Th17/Treg之间的平衡可能成为治疗RA的新方法。该文将对Th17/Treg平衡在RA发生发展中的调节作用作一综述。展开更多
To investigate the role of IL-17 in the overproduction of autoantibodies and IL-6 overexpression by peripheral blood mononuclear cells (PBMC) of lupus nephritis (LN) patients Methods Fifteen consecutively hospitaliz...To investigate the role of IL-17 in the overproduction of autoantibodies and IL-6 overexpression by peripheral blood mononuclear cells (PBMC) of lupus nephritis (LN) patients Methods Fifteen consecutively hospitalized LN patients were selected as subjects and 15 healthy adults as normal controls PBMC were obtained by Ficoll density gradient centrifugation IgG, anti-dsDNA antibody and IL-6 protein levels were assessed using enzyme-linked immunosorbent assays (ELISA) on the supernatant of cul tured PBMC of LN patients or normal controls IL-6 mRNA levels in PBMC were measured using reverse transcription-polymerase chain reaction (RT-PCR) Results In medium culture, IgG, anti-dsDNA and IL-6 protein levels of the supernatant of PBMC from LN patients were significantly higher than those from normal controls (1492 1±73 2 ng/ml vs 636 7±51 9 ng/ml for IgG, 306 6±53 7 IU/ml vs 95 8±11 6 IU/ml for anti-dsDNA and 50 92±15 92 ng/ml vs 1 77±0 73 ng/ml for IL-6, all P<0 001) In LN patients, IgG, anti-dsDNA and IL-6 protein levels were higher in the supernatants of PBMC in the IL-17-stimulated culture than the medium culture, but in normal controls, only the IL-6 protein levels were significantly higher The increase in IgG, anti-dsDNA and IL-6 protein levels induced by IL-17 was dose-dependent and could be completely blocked by IL-17 monoclonal antibody mIgG 28 and partially blocked by dexamethasone Similarly, IL-6 mRNA overexpression of PBMC in LN patients or normal controls induced by IL-17 was both dose- and time-dependent During medium culture, IL-6 mRNA levels in LN patients were significantly higher than those in normal controls (1 80±0 11 vs 0 36±0 07) During stimulation with IL-17, IL-6 mRNA levels in LN patients were higher than those in normal controls (3 21±0 24 vs 1 30±0 14, P<0 05) and also significantly higher when comparing the stimulated culture with the medium culture either in LN patients or normal control Conclusions IL-17 may play an important role展开更多
文摘CD4＋ helper T （TH） cells play crucial roles in immune responses. Recently a novel subset of TH cells, termed THIL-17, TH 17 or inflammatory TH （THi）, has been identified as critical mediators of tissue inflammation. These cells produce IL-17 （also called IL-17A） and IL-17F, two most homologous cytokines sharing similar regulations. Here we report that when overexpressed in 293T cells, IL-17 and IL-17F form not only homodimers but also heterodimers, which we name as IL-17A/F. Fully differentiated mouse THi cells also naturally secrete IL-17A/F as well as IL-17 and IL-17F homodimeric cytokines. Recombinant IL-17A/F protein exhibits intermediate levels of potency in inducing IL-6 and KC （CXCL 1） as compared to homodimeric cytokines. IL-17A/F regulation of IL-6 and KC expression is dependent on IL-17RA and TRAF6. Thus, IL-17A/F cytokine represents another mechanism whereby T cells regulate inflammatory responses and may serve as a novel target for treating various immune-mediated diseases.
基金Thisstudywassuportedfromgrantsfor211keyprojectsofSunYatSenUniversityofMedicalSciences (No .981 51 7)
文摘To investigate the role of IL-17 in the overproduction of autoantibodies and IL-6 overexpression by peripheral blood mononuclear cells (PBMC) of lupus nephritis (LN) patients Methods Fifteen consecutively hospitalized LN patients were selected as subjects and 15 healthy adults as normal controls PBMC were obtained by Ficoll density gradient centrifugation IgG, anti-dsDNA antibody and IL-6 protein levels were assessed using enzyme-linked immunosorbent assays (ELISA) on the supernatant of cul tured PBMC of LN patients or normal controls IL-6 mRNA levels in PBMC were measured using reverse transcription-polymerase chain reaction (RT-PCR) Results In medium culture, IgG, anti-dsDNA and IL-6 protein levels of the supernatant of PBMC from LN patients were significantly higher than those from normal controls (1492 1±73 2 ng/ml vs 636 7±51 9 ng/ml for IgG, 306 6±53 7 IU/ml vs 95 8±11 6 IU/ml for anti-dsDNA and 50 92±15 92 ng/ml vs 1 77±0 73 ng/ml for IL-6, all P<0 001) In LN patients, IgG, anti-dsDNA and IL-6 protein levels were higher in the supernatants of PBMC in the IL-17-stimulated culture than the medium culture, but in normal controls, only the IL-6 protein levels were significantly higher The increase in IgG, anti-dsDNA and IL-6 protein levels induced by IL-17 was dose-dependent and could be completely blocked by IL-17 monoclonal antibody mIgG 28 and partially blocked by dexamethasone Similarly, IL-6 mRNA overexpression of PBMC in LN patients or normal controls induced by IL-17 was both dose- and time-dependent During medium culture, IL-6 mRNA levels in LN patients were significantly higher than those in normal controls (1 80±0 11 vs 0 36±0 07) During stimulation with IL-17, IL-6 mRNA levels in LN patients were higher than those in normal controls (3 21±0 24 vs 1 30±0 14, P<0 05) and also significantly higher when comparing the stimulated culture with the medium culture either in LN patients or normal control Conclusions IL-17 may play an important role
