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research
Induction of peripheral tolerance in ongoing autoimmune inflammation requires interleukin 27 signaling in dendritic cells
Authors
Elisabeth R. Mari
Jason N. Moore
Javad Rasouli
Rodolfo Thome
Publication date
27 October 2017
Publisher
Jefferson Digital Commons
Doi
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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Last time updated on 30/12/2017
Jefferson Digital Commons
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:jdc.jefferson.edu:neurolog...
Last time updated on 20/11/2017