{"doi":"10.1126/sciadv.ads3728","title":"Mac-1 regulates disease stage–specific immunosuppression via the nitric oxide pathway in autoimmune disease","abstract":"Integrin Mac-1 plays a critical role in the development of multiple sclerosis (MS); however, the underlying mechanism is not fully understood. Here, we developed a myeloid-specific Mac-1–deficient mouse. Using an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, we report that Mac-1 on myeloid cells is key to disease development. Our data reveal that myeloid-specific Mac-1 significantly increases EAE severity and hinders disease regression. Loss of Mac-1 increases Gr-1 + cells in peripheral tissues and the CNS and preferably accelerates the transition of Ly6C hi monocytes from a pro-inflammatory to an immunosuppressive phenotype in a disease stage–dependent manner. Mechanistically, our results demonstrate that Mac-1 suppresses interferon-γ production and prevents monocytes from acquiring immunosuppressive functions by reducing the expression of iNOS, IDO, and CD84. Administration of a NOS-specific inhibitor in Mac-1–deficient EAE mice abolishes disease regression. These insights could help develop Mac-1–targeting strategies for better treatment of MS.","journal":"Science Advances","year":2025,"id":544124,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1434401,"name":"Chunzhang Cao","orcid":null,"position":1,"is_corresponding":false},{"id":1433953,"name":"Vishnuprabu Durairaj Pandian","orcid":"0000-0003-0142-9565","position":2,"is_corresponding":false},{"id":53866,"name":"H Ye","orcid":null,"position":3,"is_corresponding":false},{"id":1375637,"name":"Hongxia Chen","orcid":"0000-0002-2159-3381","position":4,"is_corresponding":false},{"id":1433954,"name":"Li Zhang","orcid":"0000-0003-4659-4724","position":5,"is_corresponding":false},{"id":1433952,"name":"Wei Wang","orcid":"0000-0002-0799-8171","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:53:08.338070Z","pmid":"40344054","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":[]}