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Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion.

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Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion. / Rangachari, Manu; Zhu, Chen; Sakuishi, Kaori; Xiao, Sheng; Karman, Jozsef; Chen, Andrew; Angin, Mathieu; Wakeham, Andrew; Greenfield, Edward A; Sobel, Raymond A; Okada, Hitoshi; McKinnon, Peter J; Mak, Tak W; Addo, Marylyn; Anderson, Ana C; Kuchroo, Vijay K.

in: NAT MED, Jahrgang 18, Nr. 9, 9, 2012, S. 1394-1400.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Rangachari, M, Zhu, C, Sakuishi, K, Xiao, S, Karman, J, Chen, A, Angin, M, Wakeham, A, Greenfield, EA, Sobel, RA, Okada, H, McKinnon, PJ, Mak, TW, Addo, M, Anderson, AC & Kuchroo, VK 2012, 'Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion.', NAT MED, Jg. 18, Nr. 9, 9, S. 1394-1400. <http://www.ncbi.nlm.nih.gov/pubmed/22863785?dopt=Citation>

APA

Rangachari, M., Zhu, C., Sakuishi, K., Xiao, S., Karman, J., Chen, A., Angin, M., Wakeham, A., Greenfield, E. A., Sobel, R. A., Okada, H., McKinnon, P. J., Mak, T. W., Addo, M., Anderson, A. C., & Kuchroo, V. K. (2012). Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion. NAT MED, 18(9), 1394-1400. [9]. http://www.ncbi.nlm.nih.gov/pubmed/22863785?dopt=Citation

Vancouver

Rangachari M, Zhu C, Sakuishi K, Xiao S, Karman J, Chen A et al. Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion. NAT MED. 2012;18(9):1394-1400. 9.

Bibtex

@article{0d62e67fcb2044acad863d67b5bdd647,
title = "Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion.",
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 (TH1) 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-3hi, interferon-? (IFN-?)loCD4+ 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.",
keywords = "Animals, Humans, Mice, Mice, Knockout, Flow Cytometry, Statistics, Nonparametric, Transduction, Genetic, HEK293 Cells, Genetic Vectors, Real-Time Polymerase Chain Reaction, Membrane Proteins/*metabolism, DNA-Binding Proteins/genetics, Transcription Factors/genetics, Autoimmunity/*immunology, Cell Death/*immunology, Homeodomain Proteins/genetics, Molecular Chaperones/genetics/*immunology/metabolism, Retroviridae, T-Lymphocytes/*immunology/metabolism, Animals, Humans, Mice, Mice, Knockout, Flow Cytometry, Statistics, Nonparametric, Transduction, Genetic, HEK293 Cells, Genetic Vectors, Real-Time Polymerase Chain Reaction, Membrane Proteins/*metabolism, DNA-Binding Proteins/genetics, Transcription Factors/genetics, Autoimmunity/*immunology, Cell Death/*immunology, Homeodomain Proteins/genetics, Molecular Chaperones/genetics/*immunology/metabolism, Retroviridae, T-Lymphocytes/*immunology/metabolism",
author = "Manu Rangachari and Chen Zhu and Kaori Sakuishi and Sheng Xiao and Jozsef Karman and Andrew Chen and Mathieu Angin and Andrew Wakeham and Greenfield, {Edward A} and Sobel, {Raymond A} and Hitoshi Okada and McKinnon, {Peter J} and Mak, {Tak W} and Marylyn Addo and Anderson, {Ana C} and Kuchroo, {Vijay K}",
year = "2012",
language = "English",
volume = "18",
pages = "1394--1400",
journal = "NAT MED",
issn = "1078-8956",
publisher = "NATURE PUBLISHING GROUP",
number = "9",

}

RIS

TY - JOUR

T1 - Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion.

AU - Rangachari, Manu

AU - Zhu, Chen

AU - Sakuishi, Kaori

AU - Xiao, Sheng

AU - Karman, Jozsef

AU - Chen, Andrew

AU - Angin, Mathieu

AU - Wakeham, Andrew

AU - Greenfield, Edward A

AU - Sobel, Raymond A

AU - Okada, Hitoshi

AU - McKinnon, Peter J

AU - Mak, Tak W

AU - Addo, Marylyn

AU - Anderson, Ana C

AU - Kuchroo, Vijay K

PY - 2012

Y1 - 2012

N2 - 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 (TH1) 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-3hi, interferon-? (IFN-?)loCD4+ 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.

AB - 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 (TH1) 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-3hi, interferon-? (IFN-?)loCD4+ 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.

KW - Animals

KW - Humans

KW - Mice

KW - Mice, Knockout

KW - Flow Cytometry

KW - Statistics, Nonparametric

KW - Transduction, Genetic

KW - HEK293 Cells

KW - Genetic Vectors

KW - Real-Time Polymerase Chain Reaction

KW - Membrane Proteins/metabolism

KW - DNA-Binding Proteins/genetics

KW - Transcription Factors/genetics

KW - Autoimmunity/immunology

KW - Cell Death/immunology

KW - Homeodomain Proteins/genetics

KW - Molecular Chaperones/genetics/immunology/metabolism

KW - Retroviridae

KW - T-Lymphocytes/immunology/metabolism

KW - Animals

KW - Humans

KW - Mice

KW - Mice, Knockout

KW - Flow Cytometry

KW - Statistics, Nonparametric

KW - Transduction, Genetic

KW - HEK293 Cells

KW - Genetic Vectors

KW - Real-Time Polymerase Chain Reaction

KW - Membrane Proteins/metabolism

KW - DNA-Binding Proteins/genetics

KW - Transcription Factors/genetics

KW - Autoimmunity/immunology

KW - Cell Death/immunology

KW - Homeodomain Proteins/genetics

KW - Molecular Chaperones/genetics/immunology/metabolism

KW - Retroviridae

KW - T-Lymphocytes/immunology/metabolism

M3 - SCORING: Journal article

VL - 18

SP - 1394

EP - 1400

JO - NAT MED

JF - NAT MED

SN - 1078-8956

IS - 9

M1 - 9

ER -