Microbial Flora Drives Interleukin 22 Production in Intestinal NKp46+ Cells that Provide Innate Mucosal Immune Defense

Naoko Satoh-Takayama, Christian A.J. Vosshenrich, Sarah Lesjean-Pottier, Shinichiro Sawa, Matthias Lochner, Frederique Rattis, Jean Jacques Mention, Kader Thiam, Nadine Cerf-Bensussan, Ofer Mandelboim, Gerard Eberl, James P. Di Santo

Research output: Contribution to journalArticlepeer-review

856 Citations (Scopus)


Natural killer (NK) cells are innate lymphocytes with spontaneous antitumor activity, and they produce interferon-γ (IFN-γ) that primes immune responses. Whereas T helper cell subsets differentiate from naive T cells via specific transcription factors, evidence for NK cell diversification is limited. In this report, we characterized intestinal lymphocytes expressing the NK cell natural cytotoxicity receptor NKp46. Gut NKp46+ cells were distinguished from classical NK cells by limited IFN-γ production and absence of perforin, whereas several subsets expressed the nuclear hormone receptor retinoic acid receptor-related orphan receptor t (RORγt) and interleukin-22 (IL-22). Intestinal NKp46+IL-22+ cells were generated via a local process that was conditioned by commensal bacteria and required RORγt. Mice lacking IL-22-producing NKp46+ cells showed heightened susceptibility to the pathogen Citrobacter rodentium, consistent with a role for intestinal NKp46+ cells in immune protection. RORγt-driven diversification of intestinal NKp46+ cells thereby specifies an innate cellular defense mechanism that operates at mucosal surfaces.

Original languageEnglish
Pages (from-to)958-970
Number of pages13
Issue number6
Publication statusPublished - Dec 19 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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