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Title: | EphrinB1 and EphrinB2 regulate T cell chemotaxis and migration in experimental autoimmune encephalomyelitis and multiple sclerosis | Authors: | Luo, Hongyu BROUX, Bieke Wang, Xuehai HUANG, Yanru Ghannam, Soufiane Jin, Wei Larochelle, Catherine Prat, Alexandre Wu, Jiangping |
Issue Date: | 2016 | Publisher: | ACADEMIC PRESS INC ELSEVIER SCIENCE | Source: | NEUROBIOLOGY OF DISEASE, 91, p. 292-306 | Abstract: | T cells are believed to be key effector cells in multiple sclerosis (MS). In this study, we examined the roles of T cell ephrinB1 (EFNB1) and ephrinB2 (EFNB2) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and MS. We provide evidence that animals with T cell specific double deletion of EFNB1 and EFNB2 (dKO) have reduced proliferation in response to MOG(35-55), defective Th1 and Th17 differentiations and significantly lower scores of MOG-induced EAE. We further demonstrate that dKO T cells are compromised in their ability to migrate into the CNS of EAE animals in vivo and towards multiple chemokines in vitro. Using deletion mutations, we identified a critical 11-aa EFNB1 intracellular domain segment that controls T cell chemotaxis towards CCL21. In humans, EFNB1 and EFNB2 are highly expressed in Th1 and Th17 cells and EFNB1- and EFNB2-expressing T cells are found among immune cell infiltrates in MS lesions. Reverse signaling through EFNB1 and EFNB2 in human Th17 cells enhances their migration through a monolayer of blood brain barrier endothelial cells. Our study demonstrates that expression of EFNB1 and EFNB2 is implicated in Th cell differentiation and migration to inflammatory sites in both EAE and MS. (C) 2016 Elsevier Inc. All rights reserved. | Notes: | [Luo, Hongyu; Broux, Bieke; Wang, Xuehai; Hu, Yan; Ghannam, Soufiane; Jin, Wei; Larochelle, Catherine; Prat, Alexandre; Wu, Jiangping] Univ Montreal Hosp Ctr, Res Ctr, 900 Rue St Denis, Montreal, PQ H2X 0A9, Canada. [Luo, Hongyu; Broux, Bieke; Wang, Xuehai; Hu, Yan; Ghannam, Soufiane; Jin, Wei; Larochelle, Catherine; Prat, Alexandre; Wu, Jiangping] CRCHUM, 900 Rue St Denis, Montreal, PQ H2X 0A9, Canada. [Broux, Bieke; Ghannam, Soufiane; Larochelle, Catherine; Prat, Alexandre] Univ Montreal, Fac Med, Dept Neurosci, 900 Rue St Denis, Montreal, PQ H2X 0A9, Canada. [Broux, Bieke] Hasselt Univ, Biomed Res Inst, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium. [Broux, Bieke] Transnat Univ Limburg, Sch Life Sci, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium. [Wu, Jiangping] Univ Montreal, Div Nephrol, Dept Med, Fac Med, 900 Rue St Denis, Montreal, PQ H2X 0A9, Canada. | Keywords: | Central nervous system; Ephrins; Experimental autoimmune encephalomyelitis; Migration; Multiple sclerosis; T helper cells;central nervous system; ephrins; experimental autoimmune encephalomyelitis; migration; multiple sclerosis; T helper cells | Document URI: | http://hdl.handle.net/1942/21551 | ISSN: | 0969-9961 | e-ISSN: | 1095-953X | DOI: | 10.1016/j.nbd.2016.03.013 | ISI #: | 000375885600025 | Rights: | © 2016 Elsevier Inc. All rights reserved. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2017 |
Appears in Collections: | Research publications |
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