| First Author | Velázquez FE | Year | 2019 |
| Journal | Immunology | Volume | 157 |
| Issue | 1 | Pages | 52-69 |
| PubMed ID | 30690734 | Mgi Jnum | J:273778 |
| Mgi Id | MGI:6294372 | Doi | 10.1111/imm.13047 |
| Citation | Velazquez FE, et al. (2019) Sialomucin CD43 regulates T helper type 17 cell intercellular adhesion molecule 1 dependent adhesion, apical migration and transendothelial migration. Immunology 157(1):52-69 |
| abstractText | 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 CD43 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. CD43(-/-) 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 CD43(-/-) 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. CD43(-/-) 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, CD43(-/-) Th17 cell firm arrest on ICAM-1 was comparable to that of WT Th17 cells, but CD43(-/-) 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 CD43, 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. |
