Abstract
The immune mechanisms regulating epithelial cell repair after injury remain poorly defined. We demonstrate here that lymphotoxin beta receptor (LTβR) signaling in intestinal epithelial cells promotes self-repair after mucosal damage. Using a conditional gene-targeted approach, we demonstrate that LTβR signaling in intestinal epithelial cells is essential for epithelial interleukin-23 (IL-23) production and protection against epithelial injury. We further show that epithelial-derived IL-23 promotes mucosal wound healing by inducing the IL-22-mediated proliferation and survival of epithelial cells and mucus production. Additionally, we identified CD4 - CCR6 + T-bet - RAR-related orphan receptor gamma t (RORγt) + lymphoid tissue inducer cells as the main producers of protective IL-22 after epithelial damage. Thus, our results reveal a novel role for LTβR signaling in epithelial cells in the regulation of intestinal epithelial cell homeostasis to limit mucosal damage.
Original language | English (US) |
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Pages (from-to) | 403-413 |
Number of pages | 11 |
Journal | Mucosal Immunology |
Volume | 8 |
Issue number | 2 |
DOIs | |
State | Published - Mar 14 2015 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology