--- res: bibo_abstract: - Inhibiting the alpha(4) subunit of the integrin heterodimers alpha(4)beta(1) and alpha(4)beta(7) with the monoclonal antibody natalizumab is an effective treatment for multiple sclerosis (MS). However, the pharmacological action of natalizumab is not understood conclusively. Previous studies suggested that natalizumab inhibits activation, proliferation, or extravasation of inflammatory cells. To specify which mechanisms, cell types, and alpha(4) heterodimers are affected by the antibody treatment, we studied MS-like experimental autoimmune encephalomyelitis (EAE) in mice lacking the beta(1)-integrin gene either in all hematopoietic cells or selectively in T lymphocytes. Our results show that T cells critically rely on beta(1) integrins to accumulate in the central nervous system (CNS) during EAE, whereas CNS infiltration of beta(1)-deficient myeloid cells remains unaffected, suggesting that T cells are the main target of anti-alpha(4)-antibody blockade. We demonstrate that beta(1)-integrin expression on encephalitogenic T cells is critical for EAE development, and we therefore exclude alpha(4)beta(7) as a target integrin of the antibody treatment. T cells lacking beta(1) integrin are unable to firmly adhere to CNS endothelium in vivo, whereas their priming and expansion remain unaffected. Collectively, these results suggest that the primary action of natalizumab is interference with T cell extravasation via inhibition of alpha(4)beta(1) integrins.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Martina foaf_name: Bauer, Martina foaf_surname: Bauer - foaf_Person: foaf_givenName: Cord foaf_name: Brakebusch, Cord foaf_surname: Brakebusch - foaf_Person: foaf_givenName: Caroline foaf_name: Coisne, Caroline foaf_surname: Coisne - foaf_Person: foaf_givenName: Michael K foaf_name: Michael Sixt foaf_surname: Sixt foaf_workInfoHomepage: http://www.librecat.org/personId=41E9FBEA-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-6620-9179 - foaf_Person: foaf_givenName: Hartmut foaf_name: Wekerle, Hartmut foaf_surname: Wekerle - foaf_Person: foaf_givenName: Britta foaf_name: Engelhardt, Britta foaf_surname: Engelhardt - foaf_Person: foaf_givenName: Reinhard foaf_name: Fässler, Reinhard foaf_surname: Fässler bibo_doi: 10.1073/pnas.0808909106 bibo_issue: '6' bibo_volume: 106 dct_date: 2009^xs_gYear dct_publisher: National Academy of Sciences@ dct_title: β1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity@ ...