CCR4-dependent regulatory T cell function in inflammatory bowel disease.
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of the intestine. CD4(+) T lymphocytes play an important role in both initiating and regulating intestinal inflammatory immune responses. CD4(+)CD25(+)CD45RB(low) regulatory T (T reg) cells are capable of preventing the development of colitis in a mouse model of IBD. The precise mechanism of T reg cell-mediated prevention of colitis in this model is unclear, and the role of chemokine receptors in the trafficking and function of T reg cells in this model has not been determined. We examined the role of the chemokine receptor CCR4 in in vivo trafficking and suppressive function of T reg cells in a mouse adoptive transfer model of IBD. CCR4-deficient T reg cells failed to accumulate in the mesenteric lymph nodes (MLNs) at early time points (2-5 d) after adoptive transfer, resulting in a failure to suppress the generation of pathogenic T cells and the development of colitis. Moreover, although CCR4-deficent T cells had equivalent in vitro suppressive activity and accumulated in MLNs at later time points (42-56 d), they were unable to suppress colitis. Our study demonstrates that CCR4 plays an important role in T reg cell trafficking in LNs and that this is critical for T reg cell suppressive function in vivo.
Yuan
Qian
Q
Division of Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Bromley
Shannon K
SK
Means
Terry K
TK
Jones
Krister J
KJ
Hayashi
Fumitaka
F
Bhan
Atul K
AK
Luster
Andrew D
AD
D019264:Adoptive Transfer; D000818:Animals; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054398:Receptors, CCR4 / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D054398:Receptors, CCR4