The Role of IL-17-producing Foxp3+ CD4+ T Cells in Inflammatory Bowel Disease and Colon Cancer

Wednesday, 12/06/2013  |   Inflammation, Others  |  no comments

Source: Li L, Boussiotis VA. Clinical Immunology. 15 May 2013 http://dx.doi.org/10.1016/j.clim.2013.05.003 1-s2.0-S152166161300123X-gr1 Figure 1. Induction of TReg cell mediated gut immune tolerance.In the steady state, gut immune tolerance is induced and maintained by a variety of mechanisms, which regulate the differentiation and activation of TReg cells. Some commensal bacteria can induce the differentiation of CD4+ T cells into TReg cells in a TLRs dependent manner. Clostridium spp. can induce generation of IL-10 producing TReg cells via epithelial cell-derived TGF-?, whereas Bacteroides fraglilis can induce IL-10 producing TReg cells via polysaccharide A (PSA). CD103+DC can also induce TReg cells through their ability to produce retinoic acid and TGF-?. TReg cells act on macrophage and myeloid cells to inhibit their ability to produce colitogenic cytokines including IL-12p40, Il-6 and IL-23, which are required for the differentiation of CD4+ T cells into Th1 and Th17 cells. Both Th1 and Th17 cells are associated with initiation and progression of IBD and colon cancer. TReg cells suppress inflammatory responses mainly through production of anti-inflammatory cytokines TGF-? and more importantly IL-10. The intestinal epithelium and underlying lamina propria contain T cells that play important roles in maintaining colonic homeostasis. These T cells mediate substantial and specific regulation to ensure that pathogenic microorganisms are eliminated while commensal bacteria are tolerated. There is considerable evidence supporting the notion that the altered ratio between Foxp3+CD4+ T regulatory cells and T effector cells in the colonic microenvironment might contribute to the initiation and progression of inflammation and eventually development of colon cancer. Recent findings on the heterogeneity and plasticity of T regulatory cells, such cialis 20mg buy as the identification of IL-17+Foxp3+CD4+ and the ROR?t+Foxp3+CD4+ subsets, in patients with colorectal inflammation and cancer have provided a new twist in our understanding of the pathogenesis of colonic diseases. Phenotypic and functional properties of IL-17-producing Foxp3+CD4+ T cells as well as the significant implications of these cells in the initiation and progression of colorectal diseases are discussed in this review. Increased CYP4B1 mRNA is Associated with the Inhibition of Dextran Sulfate Sodium–Induced Colitis by Caffeic Acid in Mice Ye Z, Liu Z, Henderson A, et al. Exp Biol Med (Maywood) June 2009 vol. 234 no. 6 605-616 doi: 10.3181/0901-RM-1 Susceptibility to inflammatory bowel diseases depends upon interactions between the genetics of the individual and induction of chronic mucosal inflammation. We hypothesized that administration of dietary phenolics, caffeic acid and rutin, would suppress upregulation of inflammatory markers and intestinal damage in a mouse model of colitis. Colitis was induced in C3H/ HeOuJ mice (8 weeks old, 6 male/6 female per treatment) with 1.25% dextran sulfate sodium (DSS) for 6 d in their drinking water. Rutin (1.0 mmol (524 mg)/kg in diet), caffeic acid (1.0 mmol (179 mg)/kg in diet), and hypoxoside extract (15 mg/d, an anticolitic phenolic control) were fed to the mice for 7 d before and during DSS treatment, as well as without DSS treatment. Body weight loss was prevented by rutin and caffeic acid during DSS treatment. Colon lengths in mice fed caffeic acid and hypoxoside during DSS treatment were similar to DSS-negative control. Food intake was improved and myeloperoxidase (MPO) was decreased with each phenolic treatment in DSS-treated mice compared with DSS treatment alone. Colonic mRNA expression of IL-17 and iNOS were inhibited when IL-4 was increased by each phenolic treatment combined with DSS, whereas CYP4B1 mRNA was increased only by caffeic acid in DSS-treated mice, compared with DSS treatment alone. Colonic and cecal histopathology scores of DSS-treated mice were significantly more severe (P < 0.01) than in mice fed caffeic acid before and during DSS treatment, based on mucosal height, necrosis, edema, erosion, and inflammatory cell infiltration. Although both rutin and caffeic acid suppressed the expression of selected inflammatory markers, only caffeic acid protected against DSS-induced colitis, in association with normalization of CYP4B1 expression. The inhibition of DSS-induced colitic pathology by caffeic acid was mediated by mechanisms in addition to anti-inflammatory effects that deserve further study.

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