[PDF][PDF] Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense

N Satoh-Takayama, CAJ Vosshenrich… - Immunity, 2008 - cell.com
N Satoh-Takayama, CAJ Vosshenrich, S Lesjean-Pottier, S Sawa, M Lochner, F Rattis…
Immunity, 2008cell.com
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 …
Summary
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.
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