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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)403-413
Number of pages11
JournalMucosal Immunology
Volume8
Issue number2
DOIs
StatePublished - Jan 1 2015

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Lymphotoxin beta Receptor
Interleukin-23
Epithelial Cells
Wounds and Injuries
Lymphoid Tissue
Mucus
Helper-Inducer T-Lymphocytes
Wound Healing
Homeostasis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Macho-Fernandez, E., Koroleva, E. P., Spencer, C. M., Tighe, M., Torrado, E., Cooper, A. M., ... Tumanov, A. V. (2015). Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells. Mucosal Immunology, 8(2), 403-413. https://doi.org/10.1038/mi.2014.78

Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells. / Macho-Fernandez, E.; Koroleva, E. P.; Spencer, C. M.; Tighe, M.; Torrado, E.; Cooper, A. M.; Fu, Y. X.; Tumanov, A. V.

In: Mucosal Immunology, Vol. 8, No. 2, 01.01.2015, p. 403-413.

Research output: Contribution to journalArticle

Macho-Fernandez, E, Koroleva, EP, Spencer, CM, Tighe, M, Torrado, E, Cooper, AM, Fu, YX & Tumanov, AV 2015, 'Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells', Mucosal Immunology, vol. 8, no. 2, pp. 403-413. https://doi.org/10.1038/mi.2014.78
Macho-Fernandez E, Koroleva EP, Spencer CM, Tighe M, Torrado E, Cooper AM et al. Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells. Mucosal Immunology. 2015 Jan 1;8(2):403-413. https://doi.org/10.1038/mi.2014.78
Macho-Fernandez, E. ; Koroleva, E. P. ; Spencer, C. M. ; Tighe, M. ; Torrado, E. ; Cooper, A. M. ; Fu, Y. X. ; Tumanov, A. V. / Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells. In: Mucosal Immunology. 2015 ; Vol. 8, No. 2. pp. 403-413.
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