c-kit plays a critical role in induction of intravenous tolerance in experimental autoimmune encephalomyelitis.

Publication/Presentation Date

3-1-2015

Abstract

c-kit (CD117) is a tyrosine kinase receptor found in various types of immune cells. It has been shown that c-kit plays a role in the pathogenesis of multiple sclerosis, an inflammatory demyelinating disorder of the CNS. Recent data have suggested an immunoregulatory effect of c-kit. We therefore examined the role of c-kit in autoantigen-induced i.v. tolerance in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Our results show that induction of intravenous tolerance against EAE in B6 mice is characterized by increased numbers of CD117(+) cells and altered mast cell-associated molecules in the periphery and in the CNS. W(-sh) (c-kit-deficient) mice were resistant to i.v autoantigen-induced tolerance, with increased proinflammatory cytokine production in the periphery. I.v. autoantigen in WT mice suppressed the production of proinflammatory cytokines IFN-γ and IL-6 and up-regulated the expression of FoxP3, a transcription factor of Tregs; however, in W(-sh) mice, IFN-γ and IL-6 were increased with a failure of FoxP3 induction upon i.v. autoantigen injection and is thus a mechanism for resistance to i.v. tolerance induction in these mice. We conclude that c-kit signaling has a regulatory role in i.v. tolerance and could be a target for potential immunotherapy in autoimmune disorders.

Volume

61

Issue

3

First Page

294

Last Page

302

ISSN

1559-0755

Disciplines

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

PubMedID

25588867

Department(s)

Administration and Leadership

Document Type

Article

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