Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis.
Interleukin-23 (IL-23) is an inflammatory cytokine that plays a key role in the pathogenesis of several autoimmune and inflammatory diseases. It orchestrates innate and T cell-mediated inflammatory pathways and can promote T helper 17 (Th17) cell responses. Utilizing a T cell transfer model, we showed that IL-23-dependent colitis did not require IL-17 secretion by T cells. Furthermore, IL-23-independent intestinal inflammation could develop if immunosuppressive pathways were reduced. The frequency of naive T cell-derived Foxp3+ cells in the colon increased in the absence of IL-23, indicating a role for IL-23 in controlling regulatory T cell induction. Foxp3-deficient T cells induced colitis when transferred into recipients lacking IL-23p19, showing that IL-23 was not essential for intestinal inflammation in the absence of Foxp3. Taken together, our data indicate that overriding immunosuppressive pathways is an important function of IL-23 in the intestine and could influence not only Th17 cell activity but also other types of immune responses.
Izcue
Ana
A
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.
Hue
Sophie
S
Buonocore
Sofia
S
Arancibia-Cárcamo
Carolina V
CV
Ahern
Philip P
PP
Iwakura
Yoichiro
Y
Maloy
Kevin J
KJ
Powrie
Fiona
F
D019264:Adoptive Transfer; D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D007108:Immune Tolerance / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D053759:Interleukin-23 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018836:Inflammation Mediators; D053759:Interleukin-23; D016212:Transforming Growth Factor beta; D016753:Interleukin-10