dc.contributor.author | Tang, Ruihan | |
dc.contributor.author | Acharya, Nandini | |
dc.contributor.author | Subramanian, Ayshwarya | |
dc.contributor.author | Purohit, Vinee | |
dc.contributor.author | Tabaka, Marcin | |
dc.contributor.author | Hou, Yu | |
dc.contributor.author | He, Danyang | |
dc.contributor.author | Dixon, Karen O | |
dc.contributor.author | Lambden, Connor | |
dc.contributor.author | Xia, Junrong | |
dc.contributor.author | Rozenblatt-Rosen, Orit | |
dc.contributor.author | Sobel, Raymond A | |
dc.contributor.author | Wang, Chao | |
dc.contributor.author | Regev, Aviv | |
dc.contributor.author | Anderson, Ana C | |
dc.contributor.author | Kuchroo, Vijay K | |
dc.date.accessioned | 2023-03-28T18:27:59Z | |
dc.date.available | 2023-03-28T18:27:59Z | |
dc.date.issued | 2022 | |
dc.identifier.uri | https://hdl.handle.net/1721.1/148829 | |
dc.description.abstract | <jats:p>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<jats:sub>H</jats:sub>1, T<jats:sub>H</jats:sub>17 and cytotoxic effector cells, increases regulatory T cells, and exhausted CD8<jats:sup>+</jats: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.</jats:p> | en_US |
dc.language.iso | en | |
dc.publisher | American Association for the Advancement of Science (AAAS) | en_US |
dc.relation.isversionof | 10.1126/SCIIMMUNOL.ABM0631 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Tang, Ruihan, Acharya, Nandini, Subramanian, Ayshwarya, Purohit, Vinee, Tabaka, Marcin et al. 2022. "Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function." Science Immunology, 7 (69). | |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | |
dc.contributor.department | Howard Hughes Medical Institute | |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | |
dc.relation.journal | Science Immunology | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2023-03-28T17:29:55Z | |
dspace.orderedauthors | Tang, R; Acharya, N; Subramanian, A; Purohit, V; Tabaka, M; Hou, Y; He, D; Dixon, KO; Lambden, C; Xia, J; Rozenblatt-Rosen, O; Sobel, RA; Wang, C; Regev, A; Anderson, AC; Kuchroo, VK | en_US |
dspace.date.submission | 2023-03-28T17:29:59Z | |
mit.journal.volume | 7 | en_US |
mit.journal.issue | 69 | en_US |
mit.license | OPEN_ACCESS_POLICY | |
mit.metadata.status | Authority Work and Publication Information Needed | en_US |