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

E Macho-Fernandez, E P Koroleva, C M Spencer, M Tighe, E Torrado, A M Cooper, Y-X Fu, A V Tumanov

Mucosal immunology 2015 Mar

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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 rece ptor 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.

Citation

E Macho-Fernandez, E P Koroleva, C M Spencer, M Tighe, E Torrado, A M Cooper, Y-X Fu, A V Tumanov. Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells. Mucosal immunology. 2015 Mar;8(2):403-13