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

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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.

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Acknowledgments

This study was supported by the NIH/NINDS (AR). We thank Katherine Regan for editorial assistance.

Conflict of interest

None of the co-authors has a conflict of interest to declare.

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Author notes

  1. Hongmei Li

    Present address: Department of Pathology, Children Hospital Boston, Boston, MA, 02115, USA

Authors and Affiliations

  1. Department of Neurology, Thomas Jefferson University, 901 Walnut Street, Suite 400, Philadelphia, PA, 19107, USA

    Farinaz Safavi, Hongmei Li, Patricia Gonnella, Elisabeth Rose Mari, Javad Rasouli, Guang Xian Zhang & Abdolmohamad Rostami

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  1. Farinaz Safavi
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Correspondence to Abdolmohamad Rostami.

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Farinaz Safavi and Hongmei Li contributed equally to this work.

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Safavi, F., Li, H., Gonnella, P. et al. c-kit plays a critical role in induction of intravenous tolerance in experimental autoimmune encephalomyelitis. Immunol Res 61, 294–302 (2015). https://doi.org/10.1007/s12026-015-8624-6

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