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Sialomucin CD 43 regulates T helper type 17 cell intercellular adhesion molecule 1 dependent adhesion, apical migration and transendothelial migration
Author(s) -
Velázquez Francisco E.,
Anastasiou Marina,
CarrilloSalinas Francisco J.,
Ngwenyama Njabulo,
Salvador Ane M.,
Nevers Tania,
Alcaide Pilar
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13047
Subject(s) - experimental autoimmune encephalomyelitis , microbiology and biotechnology , cell adhesion molecule , cell adhesion , cd43 , inflammation , icam 1 , biology , selectin , t cell , intercellular adhesion molecule 1 , lymphocyte function associated antigen 1 , immunology , chemistry , cell , antigen , immune system , biochemistry , cd20
Summary T helper type 17 lymphocytes (Th17 cells) infiltrate the central nervous system ( CNS ), induce inflammation and demyelination and play a pivotal role in the pathogenesis of multiple sclerosis. Sialomucin CD 43 is highly expressed in Th17 cells and mediates adhesion to endothelial selectin (E‐selectin), an initiating step in Th17 cell recruitment to sites of inflammation. CD 43 −/− mice have impaired Th17 cell recruitment to the CNS and are protected from experimental autoimmune encephalomyelitis ( EAE ), the mouse model of multiple sclerosis. However, E‐selectin is dispensable for the development of EAE , in contrast to intercellular and vascular cell adhesion molecules ( ICAM ‐1 and VCAM ‐1). We report that CD 43 −/− mice have decreased demyelination and T‐cell infiltration, but similar up‐regulation of ICAM ‐1 and VCAM ‐1 in the spinal cord, compared with wild‐type ( WT ) mice, at the initiation of EAE . CD 43 −/− Th17 cells have impaired adhesion to ICAM ‐1 under flow conditions in vitro , despite having similar expression of LFA ‐1, the main T‐cell ligand for ICAM ‐1, as WT Th17 cells. Regardless of the route of integrin activation, CD 43 −/− Th17 cell firm arrest on ICAM ‐1 was comparable to that of WT Th17 cells, but CD 43 −/− Th17 cells failed to optimally apically migrate on immobilized ICAM ‐1‐coated coverslips and endothelial cells, and to transmigrate under shear flow conditions in an ICAM ‐1‐dependent manner. Collectively, these findings unveil novel roles for CD 43, facilitating adhesion of Th17 cells to ICAM ‐1 and modulating apical and transendothelial migration, as mechanisms potentially responsible for Th17 cell recruitment to sites of inflammation such as the CNS .