Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 208, Issue 1, Pages 115-123Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20100410
Keywords
-
Categories
Funding
- The Cancer Institute of New South Wales
Ask authors/readers for more resources
Interleukin-27 (IL-27) is a cytokine known to have both proinflammatory and immunoregulatory functions. The latter appear to dominate in vivo, where IL-27 suppresses TH17 responses and promotes the differentiation of Tr1 cells expressing interferon-gamma and IL-10 and lacking forkhead box P3 (Foxp3). Accordingly, IL-27 receptor. (Il27ra)-deficient mice suffer from exacerbated immune pathology when infected with various parasites or challenged with autoantigens. Because the role of IL-27 in human and experimental mouse colitis is controversial, we studied the consequences of Il27ra deletion in the mouse T cell transfer model of colitis and unexpectedly discovered a proinflammatory role of IL-27. Absence of Il27ra on transferred T cells resulted in diminished weight loss and reduced colonic inflammation. A greater fraction of transferred T cells assumed a Foxp3(+) phenotype in the absence of Il27ra, suggesting that IL-27 functions to restrain regulatory T cell (T-reg) development. Indeed, IL-27 suppressed Foxp3 induction in vitro and in an ovalbumin-dependent tolerization model in vivo. Furthermore, effector cell proliferation and IFN-gamma production were reduced in the absence of Il27ra. Collectively, we describe a proinflammatory role of IL-27 in T cell-dependent intestinal inflammation and provide a rationale for targeting this cytokine in pathological situations that result from a breakdown in peripheral immune tolerance.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available