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IL-21/IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice.
- Source :
-
Scientific reports [Sci Rep] 2016 Aug 22; Vol. 6, pp. 31881. Date of Electronic Publication: 2016 Aug 22. - Publication Year :
- 2016
-
Abstract
- Serum level of IL-21 is increased in patients with inflammatory bowel diseases (IBD), suggesting that IL-21/IL-21 receptor (IL-21R) signaling may be involved in the pathogenesis of IBD. However, the role of IL-21/IL-21 receptor signaling plays in the pathogenesis of IBD is not very clear. In this study, using IL-21R.KO mice, we tested the role of IL-21/IL-21R signaling in the regulation of T helper cell responses during intestinal inflammation. Here we found that IL-21R.KO mice were more susceptible to DSS-induced colitis as compared with C57BL/6 mice. The spontaneous inflammatory cytokines released by macrophages in LP of colon were significantly increased, and Th2, Th17 and Treg responses were down-regulated markedly. However, Th1 responses were significantly up-regulated in IL-21R.KO mice. Meanwhile, the population of CD8(+)CD44(+)IFN-γ(+) T cells was markedly elevated in LP of inflammatory intestine of IL-21RKO mice. In vivo, after disease onset, DSS-induced intestinal inflammation was ameliorated in C57BL/6 mice treated with rIL-21. Our results demonstrate that IL-21/IL-21R signaling contributes to protection against DSS-induced acute colitis through suppression of Th1 and activation of Th2, Th17 and Treg responses in mice. Therefore, therapeutic manipulation of IL-21/IL-21R activity may allow improved immunotherapy for IBD and other inflammatory diseases associated with Th cell responses.
- Subjects :
- Animals
Colitis genetics
Colitis metabolism
Dextran Sulfate adverse effects
Disease Models, Animal
Mice
Mice, Inbred C57BL
Mice, Knockout
Mucous Membrane
Th17 Cells metabolism
Th2 Cells metabolism
Interleukin-22
Colitis chemically induced
Colitis pathology
Interleukin-21 Receptor alpha Subunit genetics
Interleukins genetics
Signal Transduction
T-Lymphocytes, Regulatory metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27545302
- Full Text :
- https://doi.org/10.1038/srep31881