Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge

Alexei V. Tumanov, Ekaterina P. Koroleva, Xiaohuan Guo, Yugang Wang, Andrei Kruglov, Sergei Nedospasov, Yang Xin Fu

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Innate lymphoid cells (ILCs) have emerged as important players, regulating the balance between protective immunity and immunopathology at mucosal surfaces. However, mechanisms that regulate ILCs' effector functions during mucosal pathogenic challenge are poorly defined. Using mice infected with the natural mouse enteric pathogen Citrobacter rodentium, we demonstrate that lymphotoxin (LT) is essential for IL-22 production by intestinal ILCs. Blocking of LTβR signaling dramatically reduced intestinal IL-22 production after C. rodentium infection. Conversely, stimulating LTβR signaling induced an IL-22 protection pathway in LT-deficient mice. Furthermore, exogenous IL-22 expression rescued LTβR-deficient mice. IL-22-producing ILCs were predominantly located in lymphoid follicles in the colon and interacted closely with dendritic cells (DCs). We find that an LT-driven positive feedback loop controls IL-22 production by RORγt + ILCs via LTβR signaling in DCs. Taken together, our data show that LTβR signaling in gut lymphoid follicles regulates IL-22 production by ILCs in response to mucosal pathogen challenge.

Original languageEnglish (US)
Pages (from-to)44-53
Number of pages10
JournalCell Host and Microbe
Volume10
Issue number1
DOIs
StatePublished - Jul 21 2011

Fingerprint

Lymphotoxin-alpha
Lymphocytes
Citrobacter rodentium
Dendritic Cells
interleukin-22
Immunity
Colon
Infection

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge. / Tumanov, Alexei V.; Koroleva, Ekaterina P.; Guo, Xiaohuan; Wang, Yugang; Kruglov, Andrei; Nedospasov, Sergei; Fu, Yang Xin.

In: Cell Host and Microbe, Vol. 10, No. 1, 21.07.2011, p. 44-53.

Research output: Contribution to journalArticle

Tumanov, Alexei V. ; Koroleva, Ekaterina P. ; Guo, Xiaohuan ; Wang, Yugang ; Kruglov, Andrei ; Nedospasov, Sergei ; Fu, Yang Xin. / Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge. In: Cell Host and Microbe. 2011 ; Vol. 10, No. 1. pp. 44-53.
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