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Immunity. 2014 Nov 20;41(5):776-88. doi: 10.1016/j.immuni.2014.10.007. Epub 2014 Nov 6.

The chemokine receptor CXCR6 controls the functional topography of interleukin-22 producing intestinal innate lymphoid cells.

Author information

1
Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France; Inserm U668, 75724 Paris, France. Electronic address: naoko@pasteur.fr.
2
Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France; Inserm U668, 75724 Paris, France.
3
Ludwig Institute for Cancer Research, Experimental Medicine Unit, Université Catholique de Louvain, Brussels, 1200 Belgium.
4
MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
5
Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France; Inserm U668, 75724 Paris, France. Electronic address: disanto@pasteur.fr.

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.

PMID:
25456160
DOI:
10.1016/j.immuni.2014.10.007
[Indexed for MEDLINE]
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