IL-6 Promotes NK Cell Production of IL-17 During Toxoplasmosis

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2010 Jan 20

PMID 20083665

Citations 102

Authors

Sara T Passos

Jonathan S Silver

Aisling C OHara

David Sehy

Jason S Stumhofer

Christopher A Hunter

Affiliations

Soon will be listed here.

Abstract

Previous studies have implicated T cell production of IL-17 in resistance to Toxoplasma gondii as well as the development of immune-mediated pathology during this infection. Analysis of C57BL/6 and C57BL/6 RAG(-/-) mice challenged with T. gondii-identified NK cells as a major innate source of IL-17. The ability of soluble Toxoplasma Ag to stimulate NK cells to produce IL-17 was dependent on the presence of accessory cells and the production of IL-6, IL-23, and TGF-beta. In contrast, these events were inhibited by IL-2, IL-15, and IL-27. Given that IL-6 was one of the most potent enhancers of NK cell production of IL-17, further studies revealed that only a subset of NK cells expressed both chains of the IL-6R, IL-6 upregulated expression of the Th17-associated transcription factor RORgammat, and that IL-6(-/-) mice challenged with T. gondii had a major defect in NK cell production of IL-17. Together, these data indicate that many of the same cytokines that regulate Th17 cells are part of a conserved pathway that also control innate production of IL-17 and identify a major role for IL-6 in the regulation of NK cell responses.

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