%0 Journal Article %T The Natural Cytotoxicity Receptor NKp46 Is Dispensable for IL-22-Mediated Innate Intestinal Immune Defense against Citrobacter rodentium %+ Cytokines et Développement Lymphoïde %+ Ludwig Institute for Cancer Research %+ The Lautenberg Center for General and Tumor Immunology [Jerusalem, Israel] %A Satoh-Takayama, Naoko %A Dumoutier, Laure %A Lesjean-Pottier, Sarah %A Ribeiro, Vera, S. G. %A Mandelboim, Ofer %A Renauld, Jean-Christophe %A Vosshenrich, Christian A. J. %A Di Santo, James, P. %Z This work was supported by grants to J.P.D. from the Institut Pasteur, INSERM, and as an “Equipe Labelisé” by the Ligue Nationale Contre le Cancer. N.S.-T. was the recipient of fellowship from The Uehara Memorial Foundation, Japan. %< avec comité de lecture %@ 0022-1767 %J Journal of Immunology %I Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists %V 183 %N 10 %P 6579-6587 %8 2009-11-15 %D 2009 %R 10.4049/jimmunol.0901935 %M 19846871 %Z Life Sciences [q-bio] %Z Life Sciences [q-bio]/ImmunologyJournal articles %X Natural cytotoxicity receptors (including NKp30, NKp44, and NKp46 in humans and NKp46 in mice) are type I transmembrane proteins that signal NK cell activation via ITAM-containing adapter proteins in response to stress- and pathogen-induced ligands. Although murine NKp46 expression (encoded by Ncr1) was thought to be predominantly restricted to NK cells, the identification of distinct intestinal NKp46(+) cell subsets that express the transcription factor Rorc and produce IL-22 suggests a broader function for NKp46 that could involve intestinal homeostasis and immune defense. Using mice carrying a GFP-modified Ncr1 allele, we found normal numbers of gut CD3(-)GFP(+) cells with a similar cell surface phenotype and subset distribution in the absence of Ncr1. Splenic and intestinal CD3(-)NKp46(+) cell subsets showed distinct patterns of cytokine secretion (IFN-gamma, IL-22) following activation via NK1.1, NKp46, IL-12 plus IL-18, or IL-23. However, IL-22 production was sharply restricted to intestinal CD3(-)GFP(+) cells with the CD127(+)NK1.1(-) phenotype and could be induced in an Ncr1-independent fashion. Because NKp46 ligands can trigger immune activation in the context of infectious pathogens, we assessed the response of wild-type and Ncr-1-deficient Rag2(-/-) mice to the enteric pathogen Citrobacter rodentium. No differences in the survival or clinical score were observed in C. rodentium-infected Rag2(-/-) mice lacking Ncr1, indicating that NKp46 plays a redundant role in the differentiation of intestinal IL-22(+) cells that mediate innate defense against this pathogen. Our results provide further evidence for functional heterogeneity in intestinal NKp46(+) cells that contrast with splenic NK cells. %G English %L pasteur-03109736 %U https://pasteur.hal.science/pasteur-03109736 %~ INSERM %~ PASTEUR %~ TEST3-HALCNRS