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CCR6 marks regulatory T cells as a colon-tropic, IL-10-producing phenotype.


ABSTRACT: Expression of CCR6 and its ligand, CCL20, are increased in the colon of humans with inflammatory bowel diseases and mice with experimental colitis; however, their role in disease pathogenesis remains obscure. In this study, we demonstrate a role for CCR6 on regulatory T (Treg) cells in the T cell-transfer model of colitis. Rag2(-/-) mice given Ccr6(-/-)CD4(+)CD45RB(high) T cells had more severe colitis with increased IFN-gamma-producing T cells, compared with the mice given wild-type cells. Although an equivalent frequency of induced/acquired Treg (iTreg) cells was observed in mesenteric lymph nodes and colon from both groups, the suppressive capacity of Ccr6(-/-) iTreg cells was impaired. Cotransfer studies of wild-type or Ccr6(-/-) Treg cells with CD4(+)CD45RB(high) T cells also showed a defect in suppression by Ccr6(-/-) Treg cells. CCR6(+) Treg cells were characterized as Ag-activated and IL-10-producing in the steady-state and preferentially migrated to the colon during inflammation. Thus, we conclude 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 by directing its function in Ag-specific, IL-10-producing iTreg cells to the inflamed colon.

SUBMITTER: Kitamura K 

PROVIDER: S-EPMC3932491 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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CCR6 marks regulatory T cells as a colon-tropic, IL-10-producing phenotype.

Kitamura Kazuya K   Farber Joshua M JM   Kelsall Brian L BL  

Journal of immunology (Baltimore, Md. : 1950) 20100818 6


Expression of CCR6 and its ligand, CCL20, are increased in the colon of humans with inflammatory bowel diseases and mice with experimental colitis; however, their role in disease pathogenesis remains obscure. In this study, we demonstrate a role for CCR6 on regulatory T (Treg) cells in the T cell-transfer model of colitis. Rag2(-/-) mice given Ccr6(-/-)CD4(+)CD45RB(high) T cells had more severe colitis with increased IFN-gamma-producing T cells, compared with the mice given wild-type cells. Alth  ...[more]

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