Dendritic cell-derived IL-32α: A novel inhibitory cytokine of nk cell function

Laurent Gorvel, Daniel Korenfeld, Thomas Tung, Eynav Klechevsky

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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-32α 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-32α 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-32α also acted on DCs by downregulating IL-15-induced IL-18 production, an important cytokine in NK cell activity. Blocking IL-32α 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-32α.

Original languageEnglish
Pages (from-to)1290-1300
Number of pages11
JournalJournal of Immunology
Volume199
Issue number4
DOIs
StatePublished - Aug 15 2017

Fingerprint Dive into the research topics of 'Dendritic cell-derived IL-32α: A novel inhibitory cytokine of nk cell function'. Together they form a unique fingerprint.

Cite this