title: IL-22 is produced by γC-independent CD25+ CCR6+ innate murine spleen cells upon inflammatory stimuli and contributes to LPS-induced lethality.
abstract: IL-22 is a Th17 cytokine that plays a key role in immune responses against extracellular bacteria. In mucosal lymphoid tissues, IL-22 production is mainly due to an IL-23-responsive NK-like cell subset that shares some markers with lymphoid tissue inducer (LTi) cells. Here, we identified a new spleen cell population responsible for IL-22 production upon either in vitro stimulation by anti-CD3 antibodies or in vivo stimulation by lipopolysaccharide (LPS) via IL-2- and an IL-23-dependent mechanisms, respectively. These cells represent 1% of spleen cells from recombination activating gene (Rag2)-deficient mice, and correspond to a discrete innate lymphoid cell population expressing CD25, CCR6 and IL-7R. This population comprises 60-70% CD4(+) cells, which produce IL-22, and are still present in common γ chain-deficient mice; the CD4(-) subset coexpresses IL-22 and IL-17, and is common γ chain-dependent. The importance of IL-22 production for the LPS-triggered response is highlighted by the fact that IL-22-deficient mice are more resistant to LPS-induced mortality.
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Belgium.
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
authors.forename: Magali
authors.initials: M
authors.lastname: de Heusch
authors.forename: Ciriana
authors.initials: C
authors.lastname: Orabona
authors.forename: Naoko
authors.initials: N
authors.lastname: Satoh-Takayama
authors.forename: Gerard
authors.initials: G
authors.lastname: Eberl
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Sirard
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D054399:Receptors, CCR6 / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; D008070:Lipopolysaccharides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054399:Receptors, CCR6; D000097043:Interleukin-22; C498126:CCR6 protein, mouse; C508018:Il2ra protein, mouse