IL-18 Drives ILC3 Proliferation and Promotes IL-22 Production via NF-κB.

Victor AR, Nalin AP, Dong W, McClory S, Wei M, Mao C, Kladney RD, Youssef Y, Chan WK, Briercheck EL, Hughes T, Scoville SD, Pitarresi JR, Chen C, Manz S, Wu LC, Zhang J, Ostrowski MC, Freud AG, Leone GW, Caligiuri MA, Yu J
J Immunol 199 2333-2342 01/01/2017

Abstract

Group 3 innate lymphoid cells (ILC3s) are important regulators of the immune system, maintaining homeostasis in the presence of commensal bacteria, but activating immune defenses in response to microbial pathogens. ILC3s are a robust source of IL-22, a cytokine critical for stimulating the antimicrobial response. We sought to identify cytokines that can promote proliferation and induce or maintain IL-22 production by ILC3s and determine a molecular mechanism for this process. We identified IL-18 as a cytokine that cooperates with an ILC3 survival factor, IL-15, to induce proliferation of human ILC3s, as well as induce and maintain IL-22 production. To determine a mechanism of action, we examined the NF-κB pathway, which is activated by IL-18 signaling. We found that the NF-κB complex signaling component, p65, binds to the proximal region of the

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