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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

926 Scopus citations


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 languageAmerican English
Pages (from-to)958-970
Number of pages13
Issue number6
StatePublished - 19 Dec 2008

Bibliographical note

Funding Information:
The work was supported by grants from the Institut Pasteur and Inserm and as an “Equipe Labelisé” by the Ligue Nationale Contre le Cancer. We would like to thank D. Guy-Grand, N. Huntington, H. Kiyono, P. Bousso, and A. Cumano for their critical comments and M. Berard and N. Winter for supplying C. rodentium and MyD88-deficient mice, respectively.




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