Reciprocal regulation of the survival and apoptosis of Th17 and Th1 cells in the colon
Version of Record online: 25 MAY 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 2, pages 333–343, February 2012
How to Cite
Ustyugova, I. V., Zhi, L. and Wu, M. X. (2012), Reciprocal regulation of the survival and apoptosis of Th17 and Th1 cells in the colon. Inflamm Bowel Dis, 18: 333–343. doi: 10.1002/ibd.21772
- Issue online: 10 JAN 2012
- Version of Record online: 25 MAY 2011
- Manuscript Accepted: 14 APR 2011
- Manuscript Received: 28 MAR 2011
- National Institutes of Health (NIH). Grant Numbers: AI050822, AI070785
- Senior Research Award from the Crohn's & Colitis Foundation of America
- Th1 and Th17 cell subsets;
The immediate early response gene X-1 (IEX-1) is a stress-inducible gene involved in the regulation of cell growth, apoptosis and inflammation.
Acute colitis was induced by treatment of IEX-1 knockout (KO) and wild type (WT) control mice with dextran sulfate sodium (DSS), whereas chronic colitis was induced in Rag−/− mice by adoptive transfer of CD4+CD45RBhi T cells isolated from the two strains of mice. The diseases and responses of lamina propria lymphocytes were analyzed in the mice.
IEX-1 KO mice produced IL-17 in the colon significantly greater than WT control mice following DSS treatment owing to better survival and differentiation of both IL-17-secreting γδ T cells and Th17 cells. The altered level of IL-17 production contributed critically to the reduced colon inflammation in IEX-1 KO mice, and administration of neutralizing anti-IL-17 antibody increased susceptibility of the animal to the disease. Strikingly, in contrast to the better survival of T cells producing IL-17, lack of IEX-1 enhanced apoptosis in proinflammatory T cells producing interferon gamma (IFN-γ). Enhanced apoptosis in Th1 cells and better survival of Th17 cells may both result in a delayed onset of colitis in Rag−/− mice receiving pathogenic CD4+CD45RBhi T cells isolated from IEX-1 KO animals compared to those mice transferred with WT counterparts
The present study demonstrates the refractoriness of IEX-1 knockout (KO) mice to DSS-induced colitis and diminished pathogenesis of IEX-1-deficient CD4+CD45RBhi T cells. These data demonstrate that IEX-1 reciprocally regulates T-cell survival and apoptosis in a subset-dependent fashion. Inhibition of IEX-1 may thus offer novel strategies for colitis treatment by simultaneous induction of apoptosis in proinflammatory Th1 cells while promoting the survival and differentiation of a protective T-cell subset. (Inflamm Bowel Dis 2011;)