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Mucosal Immunol. 2015 Mar;8(2):403-13. doi: 10.1038/mi.2014.78. Epub 2014 Sep 3.

Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells.

Author information

1
Trudeau Institute, Saranac Lake, New York, USA.
2
Department of Pathology, The University of Chicago, Chicago, Illinois, USA.

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.

PMID:
25183367
PMCID:
PMC4364000
DOI:
10.1038/mi.2014.78
[Indexed for MEDLINE]
Free PMC Article

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