Independent and interdependent immunoregulatory effects of IL-27, IFN-β, and IL-10 in the suppression of human Th17 cells and murine experimental autoimmune encephalomyelitis.

Authors

• Denise C Fitzgerald
• Zoë Fonseca-Kelly
• Melissa L Cullimore
• Pegah Safabakhsh
• Christiaan J M Saris
• Guang-Xian Zhang
• Abdolmohamad Rostami

Publication/Presentation Date

4-1-2013

Abstract

IFN-β, IL-27, and IL-10 have been shown to exert a range of similar immunoregulatory effects in murine and human experimental systems, particularly in Th1- and Th17-mediated models of autoimmune inflammatory disease. In this study we sought to translate some of our previous findings in murine systems to human in vitro models and delineate the interdependence of these different cytokines in their immunoregulatory effects. We demonstrate that human IL-27 upregulates IL-10 in T cell-activated PBMC cultures and that IFN-β drives IL-27 production in activated monocytes. IFN-β-driven IL-27 is responsible for the upregulation of IL-10, but not IL-17 suppression, by IFN-β in human PBMCs. Surprisingly, IL-10 is not required for the suppression of IL-17 by either IL-27 or IFN-β in this model or in de novo differentiating Th17 cells, nor is IL-27 signaling required for the suppression of experimental autoimmune encephalomyelitis (EAE) by IFN-β in vivo. Furthermore, and even more surprisingly, IL-10 is not required for the suppression of Th17-biased EAE by IL-27, in sharp contrast to Th1-biased EAE. In conclusion, IFN-β and IL-27 both induce human IL-10, both suppress human Th17 responses, and both suppress murine EAE. However, IL-27 signaling is not required for the therapeutic effect of IFN-β in EAE. Suppression of Th17-biased EAE by IL-27 is IL-10-independent, in contrast to its mechanism of action in Th1-biased EAE. Taken together, these findings delineate a complex set of interdependent and independent immunoregulatory mechanisms of IFN-β, IL-27, and IL-10 in human experimental models and in murine Th1- and Th17-driven autoimmunity.

Volume

190

Issue

7

First Page

3225

Last Page

3234

ISSN

1550-6606

Published In/Presented At

Fitzgerald, D. C., Fonseca-Kelly, Z., Cullimore, M. L., Safabakhsh, P., Saris, C. J., Zhang, G. X., & Rostami, A. (2013). Independent and interdependent immunoregulatory effects of IL-27, IFN-β, and IL-10 in the suppression of human Th17 cells and murine experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950), 190(7), 3225–3234. https://doi.org/10.4049/jimmunol.1200141

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

23455508

Department(s)

Administration and Leadership

Document Type

Article