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© Research
Publication : Journal of immunology (Baltimore, Md. : 1950)

The natural cytotoxicity receptor NKp46 is dispensable for IL-22-mediated innate intestinal immune defense against Citrobacter rodentium

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of immunology (Baltimore, Md. : 1950) - 21 Oct 2009

Satoh-Takayama N, Dumoutier L, Lesjean-Pottier S, Ribeiro VS, Mandelboim O, Renauld JC, Vosshenrich CA, Di Santo JP

Link to Pubmed [PMID] – 19846871

J. Immunol. 2009 Nov;183(10):6579-87

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.

http://www.ncbi.nlm.nih.gov/pubmed/19846871