In fact, iTreg cells differentiatedin vivofrom nave OT-II cells following OVA feeding expressed CCR6 at high frequencies. steady state, and preferentially migrated to the colon during inflammation. Thus, we concludes that CCR6 expression on Treg cells was required for the full function of Treg cell-mediated suppression in the T cell-transfer model of colitis. CCR6 may contribute to the regulation of colitis via the recruitment of antigen-specific, IL-10-producing iTreg cells to the inflamed colon. == Introduction == Crohns disease (CD), one of the major forms of inflammatory bowel disease (IBD), is usually believed to be caused by an abnormal immune response to commensal bacteria in a genetically susceptible host (1). While the pathogenesis of CD is still obscure, genetic approaches have uncovered major disease risk associated withCARD15/NOD2mutations (2,3); and more recently, genome-wide association studies have identified loci contain the gene forCCR6, the receptor for CCL20 (4,5), as susceptible loci for BMS-819881 CD (6,7), suggesting a possible role for cells expressing CCR6 in disease pathogenesis. Further support for this possibility includes the findings that both CCR6 and CCL20 expression are increased in the colon of both CD patients and animals with experimental colitis (811), as well as the reported expression of CCR6 on the majority of human and mouse Th17 cells (1215), which are implicated in CD pathogenesis (16). CCR6 was initially reported to be expressed on memory T, B, and immature dendritic cells (iDCs) (17,18). Recent studies have revealed unique expression of CCR6 not only on Th17, but also on IL-22-producing natural killer (NK-22) (19), IL-17-produsing / T (20), and a subpopulation of CD4+Foxp3+regulatory T (Treg) cells (2124). Interestingly, CCR6-expressing Treg cells have an effector/memory-like surface phenotype and express higher levels of IL-10 (21), compared to CCR6-unfavorable Treg cells, and are found preferentially in peripheral tissues, rather than in the spleen (24,25). Furthermore, CCR6-expressing Th17, NK-22, and IL-17-produsing / T cells are all found in the intestine (13,19,26) and the generation of Th17 cells is largely dependent on intestinal flora (26,27), suggesting the importance of CCR6 in immune homeostasis in the intestine. The CCL20-CCR6 axis has been reported to play a proinflammatory role in several murine models of autoimmune diseases, such as experimental autoimmune encephalomyelitis and psoriasis. In both of these models IL-17A/F- and/or IL-22-producing cells play a primary pathogenic role, andCcr6/mice have attenuated disease (25,2830). Moreover, administration of anti-CCR6 antibody inhibited Th17 cell-mediated arthritis in SKG mice (15), suggesting its proinflammatory role in arthritis. Recent article have also reported an association betweenCCR6polymorphism and rheumatoid arthritis susceptibility in human (5). Furthermore, there is evidence for a functional role for CCR6 in CD4-dependent allogeneic immune responses in animal models. It was shown thatCcr6/mice had a markedly diminished delayed-type hypersensitivity response induced with allogeneic splenocytes (31), and thatCcr6/CD4+T cells caused delayed, and less severe disease than wild-type CD4+T cells in allogeneic recipients in a murine model of acute graft-versus-host disease (32). In contrast to the predominantly positive effects of CCL20 and CCR6 in the induction or perpetuation of pathogenic inflammation seen in these models, their roles in the intestine appear to be more complex and poorly comprehended. Initial BMS-819881 studies revealed important roles for CCR6 in immune homeostasis of the intestine in the steady state as well as for the induction of immunity to viral and bacterial infections. CCR6 was found to be constitutively expressed by populations of B cells and dendritic cells in Peyers patches (PPs), while CCL20 Mouse monoclonal to IgG2b/IgG2a Isotype control(FITC/PE) was found predominantly produced by the epithelium overlying PPs (33). Moreover,Ccr6/mice have underdeveloped PPs and isolated lymphoid follicles (31,34), developed diminished IgA responses to rotavirus (35), and poor T cell responses toSalmonellaTyphimurium infections, consistent with a functional role BMS-819881 for CCR6 at these inductive sites. However, a possible role for CCR6 in immune regulation was also suggested by the fact thatCcr6/mice showed significantly increased TCR/ T cell subpopulations within the lamina propria (LP) of small BMS-819881 intestine, compared to WT littermates (31,35). There are several reports relevant to the mechanistic basis for the association between CCR6 and IBD. In one reportCcr6/mice were found to have had less severe colitis than WT mice after administration of dextran sodium sulfate (DSS). On the other hand, rectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced more severe colitis inCcr6/mice (36). In contrast, TNBS-induced colitis was attenuated when WT mice were treated with anti-CCL20 antibody (37). Thus, the roles for CCL20-CCR6 in IBD remain controversial. Both DSS and TNBS colitis are acute models that differ significantly from human IBD. Therefore, additional analysis is required to determine the role of CCL20-CCR6 using chronic models.