title: Phenotypic and Functional Plasticity of Murine Intestinal NKp46+ Group 3 Innate Lymphoid Cells.
abstract: Group 3 innate lymphoid cells (ILC3) actively participate in mucosal defense and homeostasis through prompt secretion of IL-17A, IL-22, and IFN-γ. Reports identify two ILC3 lineages: a CCR6(+)T-bet(-) subset that appears early in embryonic development and promotes lymphoid organogenesis and a CCR6(-)T-bet(+) subset that emerges after microbial colonization and harbors NKp46(+) ILC3. We demonstrate that NKp46 expression in the ILC3 subset is highly unstable. Cell fate mapping using Ncr1(CreGFP) × Rosa26(RFP) mice revealed the existence of an intestinal RFP(+) ILC3 subset (Ncr1(FM)) lacking NKp46 expression at the transcript and protein levels. Ncr1(FM) ILC3 produced more IL-22 and were distinguishable from NKp46(+) ILC3 by differential CD117, CD49a, DNAX accessory molecule-1, and, surprisingly, CCR6 expression. Ncr1(FM) ILC3 emerged after birth and persisted in adult mice following broad-spectrum antibiotic treatment. These results identify an unexpected phenotypic instability within NKp46(+) ILC3 that suggests a major role for environmental signals in tuning ILC3 functional plasticity.
authors.affiliation: Unité d'Immunité Innée, Institut Pasteur, 75724 Paris, France; INSERM U1223, 75724 Paris, France; Paris Diderot University, 75205 Paris, France; and.
authors.forename: Thomas
authors.identifier: 0000-0001-7030-7268
authors.initials: T
authors.lastname: Verrier
authors.affiliation: Unité d'Immunité Innée, Institut Pasteur, 75724 Paris, France; INSERM U1223, 75724 Paris, France; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Science, Yokohama 230-0045, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Satoh-Takayama
authors.affiliation: Unité d'Immunité Innée, Institut Pasteur, 75724 Paris, France; INSERM U1223, 75724 Paris, France;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Serafini
authors.affiliation: Unité d'Immunité Innée, Institut Pasteur, 75724 Paris, France; INSERM U1223, 75724 Paris, France;
authors.forename: Solenne
authors.initials: S
authors.lastname: Marie
authors.affiliation: Unité d'Immunité Innée, Institut Pasteur, 75724 Paris, France; INSERM U1223, 75724 Paris, France; james.di-santo@pasteur.fr.
authors.forename: James P
authors.identifier: 0000-0002-7146-1862
authors.initials: JP
authors.lastname: Di Santo
authors.affiliation: Unité d'Immunité Innée, Institut Pasteur, 75724 Paris, France; INSERM U1223, 75724 Paris, France;
authors.forename: Christian A J
authors.initials: CA
authors.lastname: Vosshenrich
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000276:immunology*; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology*; D010641:Phenotype
chemical_list: D000950:Antigens, Ly; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse