TY - JOUR
T1 - Microbial Flora Drives Interleukin 22 Production in Intestinal NKp46+ Cells that Provide Innate Mucosal Immune Defense
AU - Satoh-Takayama, Naoko
AU - Vosshenrich, Christian A.J.
AU - Lesjean-Pottier, Sarah
AU - Sawa, Shinichiro
AU - Lochner, Matthias
AU - Rattis, Frederique
AU - Mention, Jean Jacques
AU - Thiam, Kader
AU - Cerf-Bensussan, Nadine
AU - Mandelboim, Ofer
AU - Eberl, Gerard
AU - Di Santo, James P.
N1 - 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.
PY - 2008/12/19
Y1 - 2008/12/19
N2 - 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.
AB - 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.
KW - CELLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=57449118239&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2008.11.001
DO - 10.1016/j.immuni.2008.11.001
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C2 - 19084435
AN - SCOPUS:57449118239
SN - 1074-7613
VL - 29
SP - 958
EP - 970
JO - Immunity
JF - Immunity
IS - 6
ER -