当前位置： SCI文献检索 > INFLAMMATORY BOWEL DISEASES期刊下所有文献 > Reciprocal regulation of the survival and apoptosis of Th17 and Th1 cells in the colon.

Reciprocal regulation of the survival and apoptosis of Th17 and Th1 cells in the colon.

Abstract：

BACKGROUND:The immediate early response gene X-1 (IEX-1) is a stress-inducible gene involved in the regulation of cell growth, apoptosis and inflammation. METHODS: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(+) CD45RB(hi) T cells isolated from the two strains of mice. The diseases and responses of lamina propria lymphocytes were analyzed in the mice. RESULTS: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(+) CD45RB(hi) T cells isolated from IEX-1 KO animals compared to those mice transferred with WT counterparts CONCLUSIONS:The present study demonstrates the refractoriness of IEX-1 knockout (KO) mice to DSS-induced colitis and diminished pathogenesis of IEX-1-deficient CD4(+) CD45RB(hi) 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.

journal_name

Inflamm Bowel Dis

journal_title

Inflammatory bowel diseases

authors

Ustyugova IV,Zhi L,Wu MX

doi

10.1002/ibd.21772

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

333-43

issue

eissn

1078-0998

issn

1536-4844

journal_volume

pub_type

杂志文章

在线工具

Reciprocal regulation of the survival and apoptosis of Th17 and Th1 cells in the colon.