Journal
MUCOSAL IMMUNOLOGY
Volume 6, Issue 6, Pages 1131-1142Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2013.10
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Funding
- Ministry of Education, Cultures, Sports, Science, and Technology
- Japan Science and Technology Agency
- Grant of National Center for Global Health and Medicine [21-110, 22-205]
- Ministry of Health, Labor and Welfare of Japan
- Grants-in-Aid for Scientific Research [23590955, 25293097] Funding Source: KAKEN
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Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a TNF superfamily member, induces damage of the epithelial cells (ECs) and production of inflammatory mediaters through its receptor Fn14 in a model of acute colitis. In our current study of chronic colitis induced by repeated rectal injection of a hapten, we found that inflammation, fibrosis, and T helper 2 (Th2)-type immunity were significantly reduced in Fn14 gene knockout (KO) mice when compared with wild-type (WT) control mice. Expression of thymic stromal lymphopoietin (TSLP) was lower in Fn14 KO colon ECs than in WT ECs. TWEAK potentiates the induction of TSLP by interleukin-13 (IL-13) in colon explants from WT but not in Fn14 KO tissue. TSLP receptor KO mice exhibit milder chronic colitis, similar to that in Fn14 KO mice. TWEAK and IL-13 synergistically promote fibroblast proliferation. Thus we propose an IL-13-TWEAK/Fn14-TSLP axis as a key mechanism underlying chronic colitis with fibrosis.
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