CCR6 marks regulatory T cells as a colon-tropic, IL-10-producing phenotype.
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.
Kitamura
Kazuya
K
Mucosal Immunobiology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Farber
Joshua M
JM
Kelsall
Brian L
BL
D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054399:Receptors, CCR6 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
C106311:CCR6 protein, human; C498126:CCR6 protein, mouse; D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; C499308:Rag2 protein, mouse; D054399:Receptors, CCR6; D016753:Interleukin-10; D007371:Interferon-gamma