Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells.
Mucosal Immunol
; 8(2): 403-13, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25183367
ABSTRACT
The immune mechanisms regulating epithelial cell repair after injury remain poorly defined. We demonstrate here that lymphotoxin beta receptor (LTßR) signaling in intestinal epithelial cells promotes self-repair after mucosal damage. Using a conditional gene-targeted approach, we demonstrate that LTßR 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 LTßR signaling in epithelial cells in the regulation of intestinal epithelial cell homeostasis to limit mucosal damage.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Interleucina-23
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Receptor beta de Linfotoxina
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Mucosa Intestinal
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article