Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense.
Natural killer (NK) cells are innate lymphocytes with spontaneous antitumor activity, and they produce interferon-gamma (IFN-gamma) 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-gamma production and absence of perforin, whereas several subsets expressed the nuclear hormone receptor retinoic acid receptor-related orphan receptor t (RORgammat) and interleukin-22 (IL-22). Intestinal NKp46+IL-22+ cells were generated via a local process that was conditioned by commensal bacteria and required RORgammat. 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. RORgammat-driven diversification of intestinal NKp46+ cells thereby specifies an innate cellular defense mechanism that operates at mucosal surfaces.
Satoh-Takayama
Naoko
N
Cytokines and Lymphoid Development Unit, Institut Pasteur, Paris F-75724, France.
Vosshenrich
Christian A J
CA
Lesjean-Pottier
Sarah
S
Sawa
Shinichiro
S
Lochner
Matthias
M
Rattis
Frederique
F
Mention
Jean-Jacques
JJ
Thiam
Kader
K
Cerf-Bensussan
Nadine
N
Mandelboim
Ofer
O
Eberl
Gerard
G
Di Santo
James P
JP
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology* / Q000378:metabolism; D044082:Citrobacter rodentium / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology; D007113:Immunity, Innate; D018928:Immunity, Mucosal / Q000276:immunology; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology* / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000276:immunology / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000097043:Interleukin-22
D000950:Antigens, Ly; D007378:Interleukins; D055627:Natural Cytotoxicity Triggering Receptor 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D054353:Perforin; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D000097043:Interleukin-22; C118384:Ncr1 protein, mouse; C539901:Rorc protein, mouse