{"doi":"10.1126/sciimmunol.adg7597","title":"Integrin α3 promotes T <sub>H</sub> 17 cell polarization and extravasation during autoimmune neuroinflammation","abstract":"Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by CNS-infiltrating leukocytes, including T H 17 cells that are critical mediators of disease pathogenesis. Although targeting leukocyte trafficking is effective in treating autoimmunity, there are currently no therapeutic interventions that specifically block encephalitogenic T H 17 cell migration. Here, we report integrin α3 as a T H 17 cell–selective determinant of pathogenicity in experimental autoimmune encephalomyelitis. CNS-infiltrating T H 17 cells express high integrin α3, and its deletion in CD4 + T cells or Il17a fate-mapped cells attenuated disease severity. Mechanistically, integrin α3 enhanced the immunological synapse formation to promote the polarization and proliferation of T H 17 cells. Moreover, the transmigration of T H 17 cells into the CNS was dependent on integrin α3, and integrin α3 deficiency enhanced the retention of CD4 + T cells in the perivascular space of the blood-brain barrier. Integrin α3–dependent interactions continuously maintain T H 17 cell identity and effector function. The requirement of integrin α3 in T H 17 cell pathogenicity suggests integrin α3 as a therapeutic target for MS treatment.","journal":"Science Immunology","year":2023,"id":328739,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":511471,"name":"William E. Barclay","orcid":"0000-0002-6910-9157","position":1,"is_corresponding":false},{"id":303894,"name":"Alejandro Barrera","orcid":"0000-0001-9244-9822","position":2,"is_corresponding":false},{"id":364910,"name":"Tzu-Chieh Liao","orcid":"0000-0001-9992-8199","position":3,"is_corresponding":false},{"id":593244,"name":"Harmony R. Salzler","orcid":"0000-0002-1544-8700","position":4,"is_corresponding":false},{"id":27827,"name":"Timothy E. Reddy","orcid":"0000-0002-7629-061X","position":5,"is_corresponding":false},{"id":249988,"name":"Mari L. Shinohara","orcid":"0000-0002-6808-9844","position":6,"is_corresponding":false},{"id":282773,"name":"Maria Ciofani","orcid":"0000-0001-6472-5260","position":7,"is_corresponding":false},{"id":781807,"name":"Eunchong Park","orcid":"0000-0001-8018-664X","position":0,"is_corresponding":true}],"reference_count":117,"raw_metadata":null,"created_at":"2026-07-19T01:08:56.940647Z","pmid":"37831759","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}