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EBI2 Is Highly Expressed in Multiple Sclerosis Lesions and Promotes Early CNS Migration of Encephalitogenic CD4 T Cells.

Wanke, Florian and Moos, Sonja and Croxford, Andrew L and Heinen, André P and Gräf, Stephanie and Kalt, Bettina and Tischner, Denise and Zhang, Juan and Christen, Isabelle and Bruttger, Julia and Yogev, Nir and Tang, Yilang and Zayoud, Morad and Israel, Nicole and Karram, Khalad and Reißig, Sonja and Lacher, Sonja M and Reichhold, Christian and Mufazalov, Ilgiz A and Ben-Nun, Avraham and Kuhlmann, Tanja and Wettschureck, Nina and Sailer, Andreas W and Rajewsky, Klaus and Casola, Stefano and Waisman, Ari and Kurschus, Florian C (2017) EBI2 Is Highly Expressed in Multiple Sclerosis Lesions and Promotes Early CNS Migration of Encephalitogenic CD4 T Cells. Cell reports, 18 (5). pp. 1270-1284. ISSN 2211-1247

Abstract

Arrival of encephalitogenic T cells at inflammatory foci represents a critical step in development of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. EBI2 and its ligand, 7α,25-OHC, direct immune cell localization in secondary lymphoid organs. CH25H and CYP7B1 hydroxylate cholesterol to 7α,25-OHC. During EAE, we found increased expression of CH25H by microglia and CYP7B1 by CNS-infiltrating immune cells elevating the ligand concentration in the CNS. Two critical pro-inflammatory cytokines, interleukin-23 (IL-23) and interleukin-1 beta (IL-1β), maintained expression of EBI2 in differentiating Th17 cells. In line with this, EBI2 enhanced early migration of encephalitogenic T cells into the CNS in a transfer EAE model. Nonetheless, EBI2 was dispensable in active EAE. Human Th17 cells do also express EBI2, and EBI2 expressing cells are abundant within multiple sclerosis (MS) white matter lesions. These findings implicate EBI2 as a mediator of CNS autoimmunity and describe mechanistically its contribution to the migration of autoreactive T cells into inflamed organs.

Item Type: Article
Date Deposited: 15 Sep 2018 00:45
Last Modified: 15 Sep 2018 00:45
URI: https://oak.novartis.com/id/eprint/37559

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