{"doi":"10.1126/sciimmunol.abm0631","title":"Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function","abstract":"Dendritic cells (DCs) sense environmental cues and adopt either an immune-stimulatory or regulatory phenotype, thereby fine-tuning immune responses. Identifying endogenous regulators that determine DC function can thus inform the development of therapeutic strategies for modulating the immune response in different disease contexts. Tim-3 plays an important role in regulating immune responses by inhibiting the activation status and the T cell priming ability of DC in the setting of cancer. Bat3 is an adaptor protein that binds to the tail of Tim-3; therefore, we studied its role in regulating the functional status of DCs. In murine models of autoimmunity (experimental autoimmune encephalomyelitis) and cancer (MC38-OVA-implanted tumor), lack of Bat3 expression in DCs alters the T cell compartment-it decreases T<sub>H</sub>1, T<sub>H</sub>17 and cytotoxic effector cells, increases regulatory T cells, and exhausted CD8<sup>+</sup> tumor-infiltrating lymphocytes, resulting in the attenuation of autoimmunity and acceleration of tumor growth. We found that Bat3 expression levels were differentially regulated by activating versus inhibitory stimuli in DCs, indicating a role for Bat3 in the functional calibration of DC phenotypes. Mechanistically, loss of Bat3 in DCs led to hyperactive unfolded protein response and redirected acetyl-coenzyme A to increase cell intrinsic steroidogenesis. The enhanced steroidogenesis in Bat3-deficient DC suppressed T cell response in a paracrine manner. Our findings identified Bat3 as an endogenous regulator of DC function, which has implications for DC-based immunotherapies.","journal":"Science Immunology","year":2022,"id":7883,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-03-25","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":51573,"name":"Nandini Acharya","orcid":null,"position":1,"is_corresponding":false},{"id":2267,"name":"Ayshwarya Subramanian","orcid":"0000-0002-4134-7612","position":2,"is_corresponding":false},{"id":71071,"name":"Vinee Purohit","orcid":"0000-0001-8093-5540","position":3,"is_corresponding":false},{"id":2687,"name":"Marcin Tabaka","orcid":"0000-0002-6166-2820","position":4,"is_corresponding":false},{"id":36569,"name":"Yu Hou","orcid":"0000-0001-7875-7087","position":5,"is_corresponding":false},{"id":7815,"name":"Danyang He","orcid":"0000-0002-3613-4188","position":6,"is_corresponding":false},{"id":7816,"name":"Karen O. Dixon","orcid":"0000-0001-7811-5439","position":7,"is_corresponding":false},{"id":59143,"name":"Connor Lambden","orcid":null,"position":8,"is_corresponding":false},{"id":51572,"name":"Junrong Xia","orcid":"0000-0002-2818-1494","position":9,"is_corresponding":false},{"id":2697,"name":"Orit Rozenblatt–Rosen","orcid":"0000-0001-6313-3570","position":10,"is_corresponding":false},{"id":6938,"name":"Raymond A. Sobel","orcid":"0000-0002-0477-9002","position":11,"is_corresponding":false},{"id":6927,"name":"Chao Wang","orcid":"0000-0003-3084-6093","position":12,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":13,"is_corresponding":false},{"id":3016,"name":"Ana. C. Anderson","orcid":"0000-0002-0877-2932","position":14,"is_corresponding":false},{"id":6940,"name":"Vijay K. Kuchroo","orcid":"0000-0001-7177-2110","position":15,"is_corresponding":false},{"id":7822,"name":"Ruihan Tang","orcid":"0000-0001-5250-6239","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}