IL32 gamma activates natural killer receptor-expressing innate immune cells to produce IFN gamma via dendritic cell-derived IL12

Abstract

The inflammatory cytokine IL32 gamma acts on dendritic cells (DCs) to produce IL12 and IL6, which are involved in the differentiation of Th1 and Th17 cells. Natural killer (NK) and NKT cells play important roles in IL12-mediated adaptive immune responses, such as antitumor immunity. Herein we demonstrate the effect of IL32 gamma on the activation of NK and NKT cells. Upon IL32 gamma stimulation, splenic NK and NKT cells could be activated, and this activation was dependent on both IL12 and DCs, which was confirmed by using IL12p35 knockout and CD11c-diphtheria toxin receptor transgenic mouse models. Furthermore, IL32 gamma could induce the production of proinflammatory cytokines by NKDCs, a subset of DCs expressing NK cell markers, known to enhance NKT cell function. Unlike conventional DCs, NKDCs produced IFN gamma and TNF alpha rather than IL12 upon stimulation with IL32 gamma. Taken together, IL32 gamma will be useful as an adjuvant to boost the cytotoxicities of NK and NKT cells that play critical roles in antitumor immunity. (C) 2015 Elsevier Inc. All rights reserved.