title: The chemokine receptor CXCR6 controls the functional topography of interleukin-22 producing intestinal innate lymphoid cells.
abstract: Interleukin-22 (IL-22) plays a critical role in mucosal defense, although the molecular mechanisms that ensure IL-22 tissue distribution remain poorly understood. We show that the CXCL16-CXCR6 chemokine-chemokine receptor axis regulated group 3 innate lymphoid cell (ILC3) diversity and function. CXCL16 was constitutively expressed by CX3CR1(+) intestinal dendritic cells (DCs) and coexpressed with IL-23 after Citrobacter rodentium infection. Intestinal ILC3s expressed CXCR6 and its ablation generated a selective loss of the NKp46(+) ILC3 subset, a depletion of intestinal IL-22, and the inability to control C. rodentium infection. CD4(+) ILC3s were unaffected by CXCR6 deficiency and remained clustered within lymphoid follicles. In contrast, the lamina propria of Cxcr6(-/-) mice was devoid of ILC3s. The loss of ILC3-dependent IL-22 epithelial stimulation reduced antimicrobial peptide expression that explained the sensitivity of Cxcr6(-/-) mice to C. rodentium. Our results delineate a critical CXCL16-CXCR6 crosstalk that coordinates the intestinal topography of IL-22 secretion required for mucosal defense.
authors.affiliation: Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France; Inserm U668, 75724 Paris, France. Electronic address: naoko@pasteur.fr.
authors.forename: Naoko
authors.initials: N
authors.lastname: Satoh-Takayama
authors.affiliation: Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France; Inserm U668, 75724 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Serafini
authors.affiliation: Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France; Inserm U668, 75724 Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Verrier
authors.affiliation: Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France; Inserm U668, 75724 Paris, France.
authors.forename: Abdessalem
authors.initials: A
authors.lastname: Rekiki
authors.affiliation: Ludwig Institute for Cancer Research, Experimental Medicine Unit, Université Catholique de Louvain, Brussels, 1200 Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
authors.affiliation: Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France; Inserm U668, 75724 Paris, France. Electronic address: disanto@pasteur.fr.
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000096:biosynthesis / Q000276:immunology*; D044082:Citrobacter rodentium / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004756:Enterobacteriaceae Infections / Q000276:immunology*; D053759:Interleukin-23 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology*; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000096:biosynthesis; D054387:Receptors, CXCR / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D000950:Antigens, Ly; D000073883:CX3C Chemokine Receptor 1; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D053759:Interleukin-23; D007378:Interleukins; D055627:Natural Cytotoxicity Triggering Receptor 1; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D000097043:Interleukin-22; C471885:Cx3cr1 protein, mouse; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; C118384:Ncr1 protein, mouse