Document Type

Article

Publication Date

10-27-2017

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This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.

This article has been peer reviewed. It is the author’s final published version in Frontiers in Immunology

Volume 8, Issue OCT, October 2017, Article number 1392.

The published version is available at DOI: 10.3389/fimmu.2017.01392. Copyright © Thom et al.

Abstract

Peripheral tolerance to autoantigens is induced via suppression of self-reactive lymphocytes, stimulation of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Interleukin (IL)-27 induces tolerogenic DCs and Treg cells; however, it is not known whether IL-27 is important for tolerance induction. We immunized wild-type (WT) and IL-27 receptor (WSX-1) knockout mice with MOG35-55 for induction of experimental autoimmune encephalomyelitis and intravenously (i.v.) injected them with MOG35-55 after onset of disease to induce i.v. tolerance. i.v. administration of MOG35-55 reduced disease severity in WT mice, but was ineffective in Wsx-/- mice. IL-27 signaling in DCs was important for tolerance induction, whereas its signaling in T cells was not. Further mechanistic studies showed that IL-27-dependent tolerance relied on cooperation of distinct subsets of spleen DCs with the ability to induce T cell-derived IL-10 and IFN-γ. Overall, our data show that IL-27 is a key cytokine in antigen-induced peripheral tolerance and may provide basis for improvement of antigen-specific tolerance approaches in multiple sclerosis and other autoimmune diseases. © 2017 Thom, Moore, Mari, Rasouli, Hwang, Yoshimura, Ciric, Zhang and Rostami.

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