IL-27 regulates homeostasis of the intestinal CD4+ effector T cell pool and limits intestinal inflammation in a murine model of colitis.
IL-27 limits CD4(+) T(H)17 cell development in vitro and during inflammatory responses in the CNS. However, whether IL-27-IL-27R interactions regulate the homeostasis or function of CD4(+) T cell populations in the intestine is unknown. To test this, we examined CD4(+) T cell populations in the intestine of wild-type and IL-27R(-/-) mice. Naive IL-27R(-/-) mice exhibited a selective decrease in the frequency of IFN-gamma producing CD4(+) T(H)1 cells and an increase in the frequency of T(H)17 cells in gut-associated lymphoid tissues. Associated with elevated expression of IL-17A, IL-27R(-/-) mice exhibited earlier onset and significantly increased severity of clinical disease compared with wild-type controls in a murine model of intestinal inflammation. Rag(-/-)/IL-27R(-/-) mice were also more susceptible than Rag(-/-) mice to development of dextran sodium sulfate-induced intestinal inflammation, indicating an additional role for IL-27-IL-27R in the regulation of innate immune cell function. Consistent with this, IL-27 inhibited proinflammatory cytokine production by activated neutrophils. Collectively, these data identify a role for IL-27-IL-27R interaction in controlling the homeostasis of the intestinal T cell pool and in limiting intestinal inflammation through regulation of innate and adaptive immune cell function.
Troy
Amy E
AE
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zaph
Colby
C
Du
Yurong
Y
Taylor
Betsy C
BC
Guild
Katherine J
KJ
Hunter
Christopher A
CA
Saris
Christiaan J M
CJ
Artis
David
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006706:Homeostasis / Q000276:immunology*; D007109:Immunity; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17; D007378:Interleukins / Q000276:immunology / Q000502:physiology*; D007422:Intestines / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D018123:Receptors, Interleukin; D006377:T-Lymphocytes, Helper-Inducer / Q000473:pathology
C486767:Il27 protein, mouse; D020381:Interleukin-17; D007378:Interleukins; D018123:Receptors, Interleukin