The chemokine receptor CXCR6 controls the functional topography of interleukin-22 producing intestinal innate lymphoid cells
(2014) Immunity — Vol. 41, n° 5, p. 776-788 (2014)
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- 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.
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Satoh-Takayama, N., DiSanto, JamesP., Frankel, G., Renauld, J.-C., Rekiki, A., Verrier, T., & Serafini, N. (2014). The chemokine receptor CXCR6 controls the functional topography of interleukin-22 producing intestinal innate lymphoid cells. Immunity, 41(5), 776-788. https://doi.org/10.1016/j.immuni.2014.10.007 (Original work published 2014)