Leppkes M, Becker C, Ivanov II, et al. cells have emerged under numerous conditions. In this review article, we will summarize recent progresses of Th17 cells in regulation of intestinal homeostasis as well as in the pathogenesis of inflammatory bowel diseases. expression.71 Further exploration of the mechanisms revealed that IL-17 directly induces pIgR expression on epithelial cells in a NF-B and PI3K-dependent manner.72 Follicular helper T (Tfh) cells interact with B cells and facilitate somatic hypermutation as well as IgA class switching. Importantly, intestinal Th17 cells can also convert into Tfh cells in Peyers patches as a way to Nanchangmycin induce intestinal IgA production.79 Th17 cells can directly promote B cell IgA production as well, which is mediated mainly by IL-21, but not IL-17.80 In fact, IL-21?/? and IL-21R?/? mice with deficient IL- 21 signaling present decreased IgA level compared to wide type mice.80 IL-21 not only augments IL-4-driven IgG production, but also positively regulates transforming growth factor (TGF)-mediated IgA production by enhancing IgA class switch recombination (CSR) (Determine 2).80, 81 IL-21 also contributes to B cell mucosal homing by inducing 47. Moreover, IL-21 and IL-17 work synergistically to induce the generation of germinal centers (GCs) as transfer of Th17 cells into IL-17R?/? or IL-21R?/? mice fail to rescue the size and quantity of GCs in the draining lymph nodes and spleen. 80 Exogenous IL-21 also positively regulates IL-22 production in CD4+ T cells. IL-21R?/? mice receiving DSS developed more severe colitis compared to control mice.82 IL-22 promotion of intestinal tissue repair IL-22 has been correlated with IBD with altered expression of IL-22 found in EPHB2 colon biopsy samples from IBD patients and experimental colitis.83, 84 To date, various animal models of colitis have suggested a protective role for Th17-IL-22 axis. In DSS-induced acute colitis model, IL-22?/? mice offered worsen inflammation than wide-type control. Accordingly, IL-22?/? mice showed more severe colonic damage.84 Adoptive transfer of IL-22-deficient CD45RBhi T cells to in IL-22-treated human intestinal epithelial cell collection,75 local IL-22 gene delivery to the inflamed colonic tissues preserved the mucus layer of TCR?/? mice and alleviated the chronic colitis. Moreover, blockade of IL-22 prevented the restitution of goblet cells during the recovery phase of DSS-driven colitis, which increased the susceptibility of host to intestinal contamination.90 Gene chip analysis in combination with qPCR revealed activation of genes associated with proliferation, wound healing and anti-apoptosis downstream of IL-22, suggesting an essential role of IL-22 in tissue protection (Determine 2).91 More recently, IL-22 has been shown to promote intestinal stem cell-mediated epithelial regeneration through activation of STAT3.92 IL-26 in protection of intestinal inflammation Until recently, Th17 cells were thought to engage in bactericidal defense indirectly via conversation with epithelial cells; however, a recent statement demonstrates that Th17 cell supernatants directly restrain the growth of infected mice. studies also demonstrate the efficacy of IL-26 inhibiting the growth and/or colony formation of both gram-negative bacteria and gram-positive bacteria via pore formation. In addition, Th17-derived IL-26 is able to form potent immunogenic complex with fragments of either bacteria DNA or host self-DNA to stimulate IFN- production in plasmacytoid dendritic cells (pDCs), signifying the potential role of Th17 cells in antiviral defense.93 However, little effect of IL-26 on and fungus suggests that further studies are needed to better understand the mechanisms of IL-26-mediated killing. Th17 transdifferentiation into Tr1 cells Th17 cells are not stable, and can cease to express their signature cytokine IL-17 as well as start expressing cytokines common of other lineages under certain conditions, which has been associated with pathogenicity.96 An elegant recent study, by using novel fate-mapping mouse models to track TH17 cells during immune responses, showed that CD4+ T cells that formerly expressed IL-17 acquired an anti-inflammatory phenotype.97 The transdifferentiation of Th17 into regulatory T cells was demonstrated by changing their signature transcriptional profile and the acquisiting potent regulatory capacity. Even in steady state, about 50% of T cells which experienced expressed IL-17 previously (exTh17 cells) no longer expressed this cytokine, indicating that Th17 cells were not stable under even steady conditions. Interestingly, some of exTh17 cells expressed Nanchangmycin IL-10, which resemble Tr1 cells rather Th17 cells. Conversion Nanchangmycin of Th17 into Tr1 cells also occurred during the immune responses stimulated by anti-CD3 monoclonal antibody. Those Tr1 cells converted from exTh17 cells underwent transcriptional reprogramming during their conversion, which are similar to transcriptional programs of classic Tr1 cells rather than that of Th17 cells. When co-transferred into RAG?/? mice, Tr1 cells converted from exTh17 cells inhibited Th17 cell-mediated colitis, indicating that those T cells are functionally regulatory.