Dendritic Cell-Derived IL-32?: A Novel Inhibitory Cytokine of NK Cell Function.

ABSTRACT: Cytokines produced by dendritic cells (DCs) can largely determine the direction of immunity. Transcriptional analysis revealed that besides IL-15, IL-32 was the only other cytokine expressed by human Langerhans cells. IL-32 is a human cytokine that exists in four main isoforms. Currently, little is known about the regulation and function of the various IL-32 isoforms. In this study, we found that IL-15 is a potent inducer of IL-32? in DCs. Because IL-15 promotes NK cell activation, we investigated the interplay between IL-32 and IL-15 and their role in NK cell activity. We show that IL-32? acts on NK cells to inhibit IL-15-mediated STAT5 phosphorylation and to suppress their IL-15-induced effector molecule expression and cytolytic capacity. IL-32? also acted on DCs by downregulating IL-15-induced IL-18 production, an important cytokine in NK cell activity. Blocking IL-32? during DC:NK cell coculture enhanced NK cell effector molecule expression as well as their cytolytic capacity. Taken together, our findings suggest a feedback inhibition of IL-15-mediated NK cell activity by IL-32?.

SUBMITTER: Gorvel L 

PROVIDER: S-EPMC5544929 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature