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- Publisher Website: 10.1038/nm.2871
- Scopus: eid_2-s2.0-84868669212
- PMID: 22863785
- WOS: WOS:000308472300035
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Article: Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion
Title | Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion |
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Authors | |
Issue Date | 2012 |
Citation | Nature Medicine, 2012, v. 18, n. 9, p. 1394-1400 How to Cite? |
Abstract | T cell immunoglobulin and mucin domain-containing 3 (Tim-3) is an inhibitory receptor that is expressed on exhausted T cells during infection with HIV-1 and hepatitis C virus. By contrast, Tim-3 expression and function are defective in multiple human autoimmune diseases. However, the molecular mechanisms modulating Tim-3 function are not well understood. Here we show that human leukocyte antigen B (HLA-B)-associated transcript 3 (Bat3) binds to, and represses the function of, Tim-3. Bat3 protects T helper type 1 (T H 1) cells from galectin-9-mediated cell death and promotes both proliferation and proinflammatory cytokine production. Bat3-deficient T cells have elevated expression of exhaustion-associated molecules such as Tim-3, Lag3, Prdm1 and Pbx3, and Bat3 knockdown in myelin-antigen-specific CD4 + T cells markedly inhibits the development of experimental autoimmune encephalomyelitis while promoting the expansion of a dysfunctional Tim-3 hi, interferon-γ (IFN-γ) lo CD4 + cell population. Furthermore, expression of Bat3 is reduced in exhausted Tim-3 + T cells from mouse tumors and HIV-1-infected individuals. These data indicate that Bat3 acts as an inhibitor of Tim-3-dependent exhaustion and cell death. Bat3 may thus represent a viable therapeutic target in autoimmune disorders, chronic infections and cancers. © 2012 Nature America, Inc. All rights reserved. |
Persistent Identifier | http://hdl.handle.net/10722/292736 |
ISSN | 2023 Impact Factor: 58.7 2023 SCImago Journal Rankings: 19.045 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Rangachari, Manu | - |
dc.contributor.author | Zhu, Chen | - |
dc.contributor.author | Sakuishi, Kaori | - |
dc.contributor.author | Xiao, Sheng | - |
dc.contributor.author | Karman, Jozsef | - |
dc.contributor.author | Chen, Andrew | - |
dc.contributor.author | Angin, Mathieu | - |
dc.contributor.author | Wakeham, Andrew | - |
dc.contributor.author | Greenfield, Edward A. | - |
dc.contributor.author | Sobel, Raymond A. | - |
dc.contributor.author | Okada, Hitoshi | - |
dc.contributor.author | McKinnon, Peter J. | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Addo, Marylyn M. | - |
dc.contributor.author | Anderson, Ana C. | - |
dc.contributor.author | Kuchroo, Vijay K. | - |
dc.date.accessioned | 2020-11-17T14:57:06Z | - |
dc.date.available | 2020-11-17T14:57:06Z | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | Nature Medicine, 2012, v. 18, n. 9, p. 1394-1400 | - |
dc.identifier.issn | 1078-8956 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292736 | - |
dc.description.abstract | T cell immunoglobulin and mucin domain-containing 3 (Tim-3) is an inhibitory receptor that is expressed on exhausted T cells during infection with HIV-1 and hepatitis C virus. By contrast, Tim-3 expression and function are defective in multiple human autoimmune diseases. However, the molecular mechanisms modulating Tim-3 function are not well understood. Here we show that human leukocyte antigen B (HLA-B)-associated transcript 3 (Bat3) binds to, and represses the function of, Tim-3. Bat3 protects T helper type 1 (T H 1) cells from galectin-9-mediated cell death and promotes both proliferation and proinflammatory cytokine production. Bat3-deficient T cells have elevated expression of exhaustion-associated molecules such as Tim-3, Lag3, Prdm1 and Pbx3, and Bat3 knockdown in myelin-antigen-specific CD4 + T cells markedly inhibits the development of experimental autoimmune encephalomyelitis while promoting the expansion of a dysfunctional Tim-3 hi, interferon-γ (IFN-γ) lo CD4 + cell population. Furthermore, expression of Bat3 is reduced in exhausted Tim-3 + T cells from mouse tumors and HIV-1-infected individuals. These data indicate that Bat3 acts as an inhibitor of Tim-3-dependent exhaustion and cell death. Bat3 may thus represent a viable therapeutic target in autoimmune disorders, chronic infections and cancers. © 2012 Nature America, Inc. All rights reserved. | - |
dc.language | eng | - |
dc.relation.ispartof | Nature Medicine | - |
dc.title | Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1038/nm.2871 | - |
dc.identifier.pmid | 22863785 | - |
dc.identifier.pmcid | PMC3491118 | - |
dc.identifier.scopus | eid_2-s2.0-84868669212 | - |
dc.identifier.volume | 18 | - |
dc.identifier.issue | 9 | - |
dc.identifier.spage | 1394 | - |
dc.identifier.epage | 1400 | - |
dc.identifier.eissn | 1546-170X | - |
dc.identifier.isi | WOS:000308472300035 | - |
dc.identifier.issnl | 1078-8956 | - |