T-bet: a bridge between innate and adaptive immunity

Lazarevic, Vanja; Glimcher, Laurie H.; Lord, Graham M.

doi:10.1038/nri3536

Cited by 486T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisImmunotherapy and Immune Responses

T-bet: a bridge between innate and adaptive immunity

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Lazarevic, Vanja, Glimcher, Laurie H., Lord, Graham M.·2013·Nature Reviews Immunology

DOI 10.1038/nri3536PMC PMC6290922

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Abstract

Originally described over a decade ago as a T cell transcription factor regulating T helper 1 cell lineage commitment, T-bet is now recognized as having an important role in many cells of the adaptive and innate immune system. T-bet has a fundamental role in coordinating type 1 immune responses by controlling a network of genetic programmes that regulate the development of certain immune cells and the effector functions of others. Many of these transcriptional networks are conserved across innate and adaptive immune cells and these shared mechanisms highlight the biological functions that are regulated by T-bet.

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Signal Transducer and Activator of Transcription 4 Is Required for the Transcription Factor T-bet to Promote T Helper 1 Cell-Fate Determination
Thieu, V. T., Yu, Q., Chang, H., Yeh, N., Nguyen, E., Sehra, S., & Kaplan, M. H. (2008) · Immunity · doi:10.1016/j.immuni.2008.08.017 · Cited by 231 · see citing works
miR-29ab1-deficiency Identifies a Negative Feedback Loop Controlling Th1 Bias that is Dysregulated in Multiple Sclerosis
Smith, K., Guerau-de-Arellano, M., Costinean, S., Williams, J. L., Bottoni, A., Cox, G., Satoskar, A., Croce, C., Racke, M., Lovett-Racke, A., et al. (2012) · Journal of Immunology · doi:10.4049/jimmunol.1103171 · Cited by 193 · see citing works
Asymmetric Proteasome Segregation as a Mechanism for Unequal Partitioning of the Transcription Factor T-bet during T Lymphocyte Division
Chang, J. T., Ciocca, M. L., Kinjyo, I., Palanivel, V., McClurkin, C. E., DeJong, C. S., Mooney, E. C., Kim, J. S., Steinel, N. C., Oliaro, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.017 · Cited by 189 · see citing works
A Distal Conserved Sequence Element Controls Ifng Gene Expression by T Cells and NK Cells
Hatton, R. D., Harrington, L. E., Luther, R. J., Wakefield, T., Janowski, K. M., Oliver, J. R., Lallone, R. L., MURPHY, K. M. M., & Weaver, C. T. (2006) · Immunity · doi:10.1016/j.immuni.2006.09.007 · Cited by 185 · see citing works
Distinct requirements for T-bet in gut innate lymphoid cells
Sciumè, G., Hirahara, K., Takahashi, H., Laurence, A. D. J., Villarino, A. V., Singleton, K. L., Spencer, S. P., Wilhelm, C., Poholek, A. C., Vahedi, G., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20122097 · Cited by 179 · see citing works
The Transcription Factor GATA3 Actively Represses RUNX3 Protein-Regulated Production of Interferon-γ
Yagi, R., Junttila, I., Wei, G., Urban, J. F., Zhao, K., Paul, W. E., & Zhu, J. (2010) · Immunity · doi:10.1016/j.immuni.2010.04.004 · Cited by 174 · see citing works
Divergent transcriptional programming of class-specific B cell memory by T-bet and RORα
Wang, N. S., McHeyzer‐Williams, L. J., Okitsu, S. L., Burris, T. P., Reiner, S. L., & McHeyzer‐Williams, M. G. (2012) · Nature Immunology · doi:10.1038/ni.2294 · Cited by 169 · see citing works
The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns
Oestreich, K., Huang, A. C., & Weinmann, A. S. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20102144 · Cited by 168 · see citing works
Colitis-Associated Colorectal Cancer Driven by T-bet Deficiency in Dendritic Cells
Garrett, W. S., Punit, S., Gallini, C. A., Michaud, M., Zhang, D., Sigrist, K. S., Lord, G. M., Glickman, J. N., & Glimcher, L. H. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.07.015 · Cited by 155 · see citing works
Self-citation
Expression of T-bet by CD4 T Cells Is Essential for Resistance to Salmonella Infection
Ravindran, R., Foley, J., Stoklasek, T. A., Glimcher, L. H., & McSorley, S. J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.7.4603 · Cited by 153 · see citing works
Self-citation
IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508
Hwang, E. S., Hong, J., & Glimcher, L. H. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051044 · Cited by 151 · see citing works
Self-citation
Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expressionPreprint
Miller, S. A., Huang, A. C., Miazgowicz, M. M., Brassil, M. M., & Weinmann, A. S. (2008) · Genes & Development · doi:10.1101/gad.1689708 · Cited by 149 · see citing works
CCCTC-Binding Factor and the Transcription Factor T-bet Orchestrate T Helper 1 Cell-Specific Structure and Function at the Interferon-γ Locus
Sekimata, M., Pérez‐Melgosa, M., Miller, S. A., Weinmann, A. S., Sabo, P. J., Sandstrom, R. S., Dorschner, M. O., Stamatoyannopoulos, J. A., & Wilson, C. B. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.021 · Cited by 148 · see citing works
T-bet concomitantly controls migration, survival, and effector functions during the development of Vα14i NKT cells
Matsuda, J. L., Zhang, Q., Ndonye, R. M., Richardson, S. K., Howell, A. R., & Gapin, L. (2005) · Blood · doi:10.1182/blood-2005-08-3103 · Cited by 145 · see citing works
T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype
Mathur, A. N. (2006) · Blood · doi:10.1182/blood-2006-04-015016 · Cited by 143 · see citing works
Induction of IgG2a Class Switching in B Cells by IL-27
Yoshimoto, T., OKADA, K., Morishima, N., Kamiya, S., Owaki, T., Asakawa, M., Iwakura, Y., Fukai, F., & Mizuguchi, J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.4.2479 · Cited by 140 · see citing works
Increased Susceptibility of Mice Lacking T-bet to Infection with Mycobacterium tuberculosis Correlates with Increased IL-10 and Decreased IFN-γ Production
Sullivan, B. M., Jobe, O., Lazarevic, V., Vasquez, K. O., Bronson, R. T., Glimcher, L. H., & Kramnik, I. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.7.4593 · Cited by 139 · see citing works
Self-citation
Evolutionarily conserved sequence elements that positively regulate IFN-γ expression in T cells
Shnyreva, M., Weaver, W. M., Blanchette, M., Taylor, S. L., Tompa, M., Fitzpatrick, D. R., & Wilson, C. B. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400849101 · Cited by 137 · see citing works
STAT1-Activating Cytokines Limit Th17 Responses through Both T-bet–Dependent and –Independent Mechanisms
Villarino, A. V., Gallo, E., & Abbas, A. K. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001343 · Cited by 125 · see citing works
Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells
Wang, J. H. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26631 · Cited by 121 · see citing works
T-Bet Expression and Failure of GATA-3 Cross-Regulation Lead to Default Production of IFN-γ by γδ T Cells
Yin, Z., Chen, C.-H., Szabo, S. J., Glimcher, L. H., Ray, A., & Craft, J. E. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.4.1566 · Cited by 103 · see citing works
Self-citation
Modular Utilization of Distal cis-Regulatory Elements Controls Ifng Gene Expression in T Cells Activated by Distinct Stimuli
Balasubramani, A., Shibata, Y., Crawford, G. E., Baldwin, A. S., Hatton, R. D., & Weaver, C. T. (2010) · Immunity · doi:10.1016/j.immuni.2010.07.004 · Cited by 99 · see citing works
Increased numbers of pre-existing memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells
Joshi, N., Cui, W., Dominguez, C. X., Chen, J. H., Hand, T., & Kaech, S. (2011) · Journal of Immunology · doi:10.4049/jimmunol.1002145 · Cited by 94 · see citing works
T-Bet Plays a Key Role in NK-Mediated Control of Melanoma Metastatic Disease
Werneck, M. B. F., Lugo‐Villarino, G., Hwang, E. S., Cantor, H., & Glimcher, L. H. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.12.8004 · Cited by 84 · see citing works
Self-citation
Molecular mechanisms by which T‐bet regulates T‐helper cell commitment
Miller, S. A., & Weinmann, A. S. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00952.x · Cited by 78 · see citing works
Epigenetic and Transcriptional Programs Lead to Default IFN-γ Production by γδ T Cells
Chen, L., He, W., Kim, S. T., Tao, J., Gao, Y., Chi, H., Intlekofer, A. M., Harvey, B. P., Reiner, S. L., Yin, Z., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.5.2730 · Cited by 69 · see citing works
Stat1-Dependent Synergistic Activation of T-bet for IgG2a Production during Early Stage of B Cell Activation
Xu, W., & Zhang, J. J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.11.7419 · Cited by 67 · see citing works
The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells
Lugo‐Villarino, G., Ito, S.-I., Klinman, D. M., & Glimcher, L. H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506638102 · Cited by 60 · see citing works
Self-citation
Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue
Alcaide, P., Jones, T. G., Lord, G. M., Glimcher, L. H., Hallgren, J., Arinobu, Y., Akashi, K., Paterson, A. M., Gurish, M. A., & Luscinskas, F. W. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20060626 · Cited by 47 · see citing works
Self-citation
The Ets-1 transcription factor is required for Stat1-mediated T-bet expression and IgG2a class switching in mouse B cells
Nguyen, H. V., Mouly, E., Chemin, K., Luinaud, R., Despres, R., Fermand, J., Arnulf, B., & Bories, J.-C. (2012) · Blood · doi:10.1182/blood-2011-09-378182 · Cited by 45 · see citing works
CD8 T cells induce T-bet–dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines
Serre, K., Cunningham, A. F., Coughlan, R. E., Lino, A. C., Rot, A., Hub, E., Moser, K., Manz, R. A., Ferraro, A., Bird, R., et al. (2012) · Blood · doi:10.1182/blood-2012-03-417733 · Cited by 42 · see citing works
Lysine 313 of T-box Is Crucial for Modulation of Protein Stability, DNA Binding, and Threonine Phosphorylation of T-bet
Jang, E. J., Park, H. R., Hong, J., & Hwang, E. S. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203403 · Cited by 40 · see citing works
The Development of Airway Hyperreactivity in T-bet-Deficient Mice Requires CD1d-Restricted NKT Cells
Kim, H. Y., Pichavant, M., Matangkasombut, P., Koh, Y., Savage, P. B., DeKruyff, R. H., & Umetsu, D. T. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803339 · Cited by 34 · see citing works
Evolution of developmental functions by the Eomesodermin, T‐brain‐1, Tbx21 subfamily of T‐box genes: insights from amphioxus
Horton, A. C., & Gibson‐Brown, J. J. (2002) · Journal of Experimental Zoology · doi:10.1002/jez.10151 · Cited by 32 · see citing works
Inflammatory Bowel Disease — Live Transmission
Hecht, G. A. (2008) · New England Journal of Medicine · doi:10.1056/nejmcibr0707718 · Cited by 27 · see citing works
Transcriptional regulation of the mucosal immune system mediated by T-bet
Powell, N., Canavan, J. B., MacDonald, T. T., & Lord, G. M. (2010) · Mucosal Immunology · doi:10.1038/mi.2010.53 · Cited by 22 · see citing works
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Cytokines in inflammatory bowel disease
Neurath, M. F. (2014) · Nature Reviews Immunology · doi:10.1038/nri3661 · Cited by 2,706 · see citing works
Interleukins in cancer: from biology to therapy
Briukhovetska, D., Dörr, J., Endres, S., Libby, P., Dinarello, C., & Kobold, S. (2021) · Nature Reviews. Cancer · doi:10.1038/s41568-021-00363-z · Cited by 693 · see citing works
Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer
Yu, L., Wei, J., & Liu, P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.06.019 · Cited by 785 · see citing works
MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint Blockade.
Ebert, P. J. R., Cheung, J., Yang, Y., McNamara, E., Hong, R., Moskalenko, M., Gould, S. E., Maecker, H., Irving, B. A., Kim, J. M., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.01.024 · Cited by 713 · see citing works
“The resulting T-betEomes cells are thought to represent a ‘‘short-termmemory’’ population that produces cytokines and can self-renew or further differentiate into effector CTLs (Lazarevic et al., 2013).”
BackgroundInfluential
The foundations of immune checkpoint blockade and the ipilimumab approval decennial
Korman, A. J., Garrett-Thomson, S. C., & Lönberg, N. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00345-8 · Cited by 561 · see citing works
Age-Associated B Cells
Cancro, M. P. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-092419-031130 · Cited by 464 · see citing works
Inflammatory triggers associated with exacerbations of COPD orchestrate plasticity of group 2 innate lymphoid cells in the lungs
Silver, J. S., Kearley, J., Copenhaver, A. M., Sandén, C., Mori, M., Yu, L., Pritchard, G. H., Berlin, A. A., Hunter, C. A., Bowler, R. P., et al. (2016) · Nature Immunology · doi:10.1038/ni.3443 · Cited by 451 · see citing works
Model-Based Assessment of the Role of Uneven Partitioning of Molecular Content on Heterogeneity and Regulation of Differentiation in CD8 T-Cell Immune Responses
Girel, S., Arpin, C., Marvel, J., Gandrillon, O., & Fabien Crauste, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00230 · Cited by 390 · see citing works
“It should be noted that various works support that Eomes expression increases in effector cells progressing toward a memory phenotype (11, 15, 43), contrary to what is observed in the mRNA dataset from Immgen.”
BackgroundResultInfluential
Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer
Dong, C., Wu, J., Chen, Y., Nie, J., & Chen, C. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.628690 · Cited by 383 · see citing works
PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux
O’Donnell, J. S., Massi, D., Teng, M. W. L., & Mandalà, M. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.04.015 · Cited by 382 · see citing works
Understanding the tumor microenvironment for effective immunotherapy
Sadeghi Rad, H., Monkman, J., Warkiani, M. E., Ladwa, R., O'Byrne, K., Rezaei, N., & Kulasinghe, A. (2021) · Medicinal Research Reviews · doi:10.1002/med.21765 · Cited by 334 · see citing works
“It should be noted here that TBET is a transcription factor required for the induction of the Th1 cell phenotype.(114,115) Thus, the researchers suggested that only specific T cell subsets were targeted by ICIs.”
Background
Canonical and Non-Canonical Aspects of JAK–STAT Signaling: Lessons from Interferons for Cytokine Responses
Majoros, A., Platanitis, E., Kernbauer, E., Rosebrock, F., Müller, M. M., & Decker, T. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00029 · Cited by 325 · see citing works
“In the adaptive immunity, IFNγ plays an important role in Th1 responses, repressing the development of Th2 and Th17 T cell responses (30) and acting directly on B cells to promote class switching from IgG2 to IgG3 (32).”
Background
CRISPR activation and interference screens decode stimulation responses in primary human T cells
Schmidt, R., Steinhart, Z., Layeghi, M., Freimer, J. W., Bueno, R., Nguyen, V., Blaeschke, F., Ye, C. J., & Marson, A. (2022) · Science · doi:10.1126/science.abj4008 · Cited by 285 · see citing works
The T-box gene family: emerging roles in development, stem cells and cancer
Papaioannou, V. E. (2014) · Development · doi:10.1242/dev.104471 · Cited by 293 · see citing works
“such that susceptibility to metastatic cancers is greatly increased (Lazarevic et al., 2013).”
Background
Polyamine metabolism is a central determinant of helper T cell lineage fidelity
Puleston, D. J., Baixauli, F., Sanin, D. E., Edwards-Hicks, J., Villa, M., Kabat, A. M., Kamiński, M. M., Stanckzak, M., Weiss, H. J., Grzes, K. M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.06.007 · Cited by 295 · see citing works
“Preventing aberrant T-bet expression does not restore focused TH lineage commitment in Odc / and Dohh / CD4 T cells and supports a key role for polyamine metabolism in governing the T cell epigenome T-bet can regulate TH1 differentiation by recruiting chromatin modifying enzymes promoting permissive chromatin marks at…”
Background
β-Adrenergic Signaling in Mice Housed at Standard Temperatures Suppresses an Effector Phenotype in CD8+ T Cells and Undermines Checkpoint Inhibitor Therapy
Bucsek, M. J., Qiao, G., MacDonald, C. R., Giridharan, T., Evans, L., Niedzwecki, B., Liu, H., Kokolus, K. M., Eng, J. W.-L., Messmer, M. N., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0546 · Cited by 294 · see citing works
Update on Ankylosing Spondylitis: Current Concepts in Pathogenesis
Smith, J. A. (2014) · Current Allergy and Asthma Reports · doi:10.1007/s11882-014-0489-6 · Cited by 257 · see citing works
Dynamic expression of transcription factors T-bet and GATA-3 by regulatory T cells maintains immunotolerance
Yu, F., Sharma, S., Edwards, J., Feigenbaum, L., & Zhu, J. (2014) · Nature Immunology · doi:10.1038/ni.3053 · Cited by 249 · see citing works
CD4 T-Cell Subsets and the Pathophysiology of Inflammatory Bowel Disease
Gómez-Bris, R., Saéz, Á., Herrero‐Fernández, B., Rius, C., Sánchez-Martinez, H., & González, J. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032696 · Cited by 255 · see citing works
“Th1 cells release IFN-γ and TNF-α, which stimulate innate immune cells, such as neutrophils and macrophages, and non-immune cells, such as epithelial cells and fibroblasts [55,56].”
Background
The host immune response to gastrointestinal nematode infection in sheep
McRae, K. M., Stear, M. J., Good, B., & Keane, O. M. (2015) · Parasite Immunology · doi:10.1111/pim.12290 · Cited by 244 · see citing works
An Integrated Multi-omic Single-Cell Atlas of Human B Cell Identity
Glass, D. R., Tsai, A. G., Oliveria, J. P., Hartmann, F. J., Kimmey, S. C., Calderon, A. A., Borges, L., Glass, M. C., Wagar, L. E., Davis, M. M., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.06.013 · Cited by 232 · see citing works
T cell-mediated immunity to malaria
Kurup, S. P., Butler, N. S., & Harty, J. T. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0158-z · Cited by 242 · see citing works
Microbiota metabolite butyrate differentially regulates Th1 and Th17 cells' differentiation and function in induction of colitis
Chen, L., Sun, M., Wu, W., Yang, W., Huang, X., Xiao, Y., Ma, C., Xu, L., Yao, S., Liu, Z., et al. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izz046 · Cited by 231 · see citing works
Imprinted SARS-CoV-2-Specific Memory Lymphocytes Define Hybrid Immunity
Rodda, L. B., Morawski, P. A., Pruner, K. B., Fahning, M. L., Howard, C. A., Franko, N., Logue, J. K., Eggenberger, J., Stokes, C., Golez, I., et al. (2022) · Cell · doi:10.1016/j.cell.2022.03.018 · Cited by 191 · see citing works
“…PAMPs, directly drive T cells to upregulate the transcription factor T-bet, the master transcription factor for Th1 cells (Brinkmann et al., 1993; Lazarevic et al., 2013), and may induce the CD4+ memory T cell IFN-g and IL-10 signature we describe in PI individuals that is maintained through…”
Atypical memory B cells in human chronic infectious diseases: An interim report
Portugal, S., Obeng-Adjei, N., Moir, S. L., Crompton, P. D., & Pierce, S. K. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.07.003 · Cited by 192 · see citing works
“Although differences in IgG subclasses between mice and humans make direct comparisons difficult, in mice, T-bet is a selective inducer of IFN-γ-mediated class switching to IgG2a (70, 76, 77), which is functionally similar to human IgG1 and IgG3 in terms of FcR binding and complement fixation capacity.”
Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection
Tu, W., & Rao, S. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.02111 · Cited by 189 · see citing works
Macrophage response to hydrophilic biomaterials regulates MSC recruitment and T-helper cell populations
Hotchkiss, K. M., Clark, N. M., & Olivares-Navarrete, R. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.08.029 · Cited by 178 · see citing works
T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response
Knox, J. J., Buggert, M., Kardava, L., Seaton, K. E., Eller, M. A., Canaday, D. H., Robb, M. L., Ostrowski, M., Deeks, S. G., Slifka, M. K., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.92943 · Cited by 172 · see citing works
“T-bet is considered to function as a master regulator of Th1-type immunity (50), and T-bet is known to”
T-cells and their cytokine production: The anti-inflammatory and immunosuppressive effects of strenuous exercise
Shaw, D. M., Mérien, F., Braakhuis, A. J., & Dulson, D. K. (2017) · Cytokine · doi:10.1016/j.cyto.2017.10.001 · Cited by 176 · see citing works
Recent advances in understanding the Th1/Th2 effector choice
Butcher, M. J., & Zhu, J. (2021) · Faculty Reviews · doi:10.12703/r/10-30 · Cited by 176 · see citing works
Cutting Edge: B Cell–Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection
Barnett, B. E., Staupe, R. P., Odorizzi, P. M., Palko, O., Tomov, V. T., Mahan, A. E., Gunn, B. M., Chen, D. A., Paley, M., Alter, G., et al. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1500368 · Cited by 171 · see citing works
“T-bet controls antiviral gene programs in CD4 and CD8 T cells, NK cells, and group 1 innate lymphoid cells (19).”
Background
Malaria-induced interferon-γ drives the expansion of Tbethi atypical memory B cells
Obeng-Adjei, N., Portugal, S., Holla, P., Li, S., Sohn, H., Ambegaonkar, A. A., Skinner, J., Bowyer, G., Doumbo, O. K., Traoré, B., et al. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006576 · Cited by 165 · see citing works
“In mice, T-bet is known to be a selective inducer of IFN-γ-mediated IgG2a class switching in B cells.”
Background
CNS Repair Requires Both Effector and Regulatory T Cells with Distinct Temporal and Spatial Profiles
Rapôso, C., Graubardt, N., Cohen, M., Eitan, C., London, A., Berkutzki, T., & Schwartz, M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0076-14.2014 · Cited by 161 · see citing works
“In addition, we observed lower numbers of NK and NK T cells, in line with the role of TBX21 in the development and maturation of NK cells (Townsend et al., 2004; Lazarevic et al., 2013); however, these cells represented minute populations at the injured spinal cord (1.”
BackgroundInfluential
Transcription Factor T-bet Orchestrates Lineage Development and Function in the Immune System
Kallies, A., & Good‐Jacobson, K. L. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.02.003 · Cited by 157 · see citing works
“Their differentiation is driven by a set of transcriptional ‘master’ regulators, including T-bet, GATA binding protein 3 (GATA3) and RAR-related orphan receptor gamma, thymus-specific isoform (RORgt), which control the development of Th1, Th2 and Th17 cells, respectively [4,5].”
Background
Age‐associated B cells: key mediators of both protective and autoreactive humoral responses
Naradikian, M. S., Hao, Y., & Cancro, M. P. (2015) · Immunological Reviews · doi:10.1111/imr.12380 · Cited by 152 · see citing works
Comprehensive identification of arginine methylation in primary T cells reveals regulatory roles in cell signalling
Geoghegan, V., Guo, A., Trudgian, D. C., Thomas, B., & Acuto, O. (2015) · Nature Communications · doi:10.1038/ncomms7758 · Cited by 150 · see citing works
Eomesodermin promotes the development of type 1 regulatory T (T R 1) cells
Zhang, P., Lee, J. S., Gartlan, K. H., Schuster, I. S., Comerford, I., Varelias, A., Ullah, M. A., Vučković, S., Koyama, M., Kuns, R. D., et al. (2017) · Science Immunology · doi:10.1126/sciimmunol.aah7152 · Cited by 150 · see citing works
“Eomes can be regulated by T-bet in a Runx-3 dependent manner and the differential expression of these two T-box transcription factors is critical for the differentiation of CD8+ T cells (47, 48).”
Background
Dissecting the Heterogeneity in T-Cell Mediated Inflammation in IBD
Tindemans, I., Joosse, M. E., & Samsom, J. N. (2020) · Cells · doi:10.3390/cells9010110 · Cited by 143 · see citing works
“Th1 cells produce interferon gamma (IFN-γ) and Tumor Necrosis Factor alpha (TNF-α) which activate innate immune cells among which phagocytes such as neutrophils and macrophages and structural tissue cells such as epithelial cells and myofibroblasts [48,49].”
Background
Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria
Yang, R., Mele, F., Worley, L., Langlais, D., Rosain, J., Benhsaien, I., Elarabi, H., Croft, C. A., Doisne, J., Zhang, P., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.046 · Cited by 138 · see citing works
Self-citation
T‐bet+ memory B cells: Generation, function, and fate
Knox, J. J., Myles, A., & Cancro, M. P. (2019) · Immunological Reviews · doi:10.1111/imr.12736 · Cited by 135 · see citing works
T-bet Transcription Factor Promotes Antibody-Secreting Cell Differentiation by Limiting the Inflammatory Effects of IFN-γ on B Cells
Stone, S. L., Peel, J. N., Scharer, C. D., Risley, C. A., Chisolm, D. A., Schultz, M. D., Yu, B., Ballesteros‐Tato, A., Wojciechowski, W., Mousseau, B. J., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.004 · Cited by 132 · see citing works
“, 2012) and by repressing alternate cell fate (Lazarevic et al., 2013) and type I interferon (IFN)-induced inflammatory gene programs (Iwata et al.”
Background
The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination
Yu, F., Sharma, S., Jankovic, D. L., Gurram, R. K., Su, P., Hu, G., Li, R., Rieder, S. A., Zhao, K., Sun, B., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20170155 · Cited by 130 · see citing works
“Transcription factor T-bet is the master transcriptional regulator for the development and functions of Th1 cells (Szabo et al., 2000; Lazarevic et al., 2013).”
Background
Single-cell transcriptional analysis reveals ILC-like cells in zebrafish
Hernández, P. P., Strzelecka, P. M., Athanasiadis, E. I., Hall, D., Robalo, A. F., Collins, C., Boudinot, P., Levraud, J., & Cvejic, A. (2018) · Science Immunology · doi:10.1126/sciimmunol.aau5265 · Cited by 130 · see citing works
Delta-24-RGD Oncolytic Adenovirus Elicits Anti-Glioma Immunity in an Immunocompetent Mouse Model
Jiang, H., Clise-Dwyer, K., Ruisaard, K. E., Fan, X., Tian, W., Gumin, J., Lamfers, M. L. M., Kleijn, A., Lang, F. F., Yung, W.-K. A., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097407 · Cited by 127 · see citing works
“Our data show the intratumoral injections of Delta-24-RGD break the immunosuppressive balance within the tumor and stir up the stimulators for a robust Th1 immune response as indicated by the increment of T-bet expressing cells, including NK cells, in the tumor (figure 2A and B) [28].”
Background
CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis
Roan, F., Stoklasek, T. A., Whalen, E., Molitor, J. A., Bluestone, J. A., Buckner, J. H., & Ziegler, S. F. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1501491 · Cited by 127 · see citing works
Immunomodulatory effects of BRAF and MEK inhibitors: Implications for Melanoma therapy
Kuske, M., Westphal, D., Wehner, R., Schmitz, M., Beissert, S., Praetorius, C., & Meier, F. E. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.08.019 · Cited by 127 · see citing works
Nanoparticle formulated vaccines: opportunities and challenges
Lung, P., Yang, J., & Li, Q. (2020) · Nanoscale · doi:10.1039/c9nr08958f · Cited by 126 · see citing works
Immunological memory cells
Ratajczak, W., Niedźwiedzka‐Rystwej, P., Tokarz–Deptuła, B., & Deptuła, W. (2018) · Central European Journal of Immunology · doi:10.5114/ceji.2018.77390 · Cited by 121 · see citing works
“In the case of IgG2a and IgA Bm lymphocytes, their survival also depends on T-bet (T-box transcription factor) [78, 92], crucial for Th1 development and functioning, and RORα (retinoic acid receptor-related orphan receptor α) [78, 92].”
Background
Immunologic Overlap of Helper T-Cell Subtypes 17 and 22 in Erythrodermic Psoriasis and Atopic Dermatitis
Moy, A. P., Murali, M. R., Kroshinsky, D., Duncan, L. M., & Nazarian, R. M. (2015) · JAMA Dermatology · doi:10.1001/jamadermatol.2015.2 · Cited by 122 · see citing works
New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function
Fu, S., Yeh, L., Chu, C., Yen, B., & Sytwu, H. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0354-8 · Cited by 119 · see citing works
“After an infection is cleared, the MPECs will generate memory CD8 T cells that can be either EM (KLRG1IL-7RαCD62LCCR7) or CM (KLRG1IL7RαCD62LCCR7) cells [22].”
Background
FGL2 promotes tumor progression in the CNS by suppressing CD103+ dendritic cell differentiation
Yan, J., Zhao, Q., Gabrusiewicz, K. R., Kong, L.-Y., Xia, X., Wang, J., Ott, M., Xu, J., Davis, R. E., Huo, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08271-x · Cited by 119 · see citing works
Key mediators in the immunopathogenesis of allergic asthma
Hall, S. C., & Agrawal, D. K. (2014) · International Immunopharmacology · doi:10.1016/j.intimp.2014.05.034 · Cited by 119 · see citing works
Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8+ T cells that induce GVHD without antileukemic effects
Gartlan, K. H., Markey, K. A., Varelias, A., Bunting, M. D., Koyama, M., Kuns, R. D., Raffelt, N. C., Olver, S. D., Lineburg, K. E., Cheong, M., et al. (2015) · Blood · doi:10.1182/blood-2015-01-622662 · Cited by 115 · see citing works
“CD8YFP T-cells displayed significantly reduced expression of the short-lived effector cell (SLEC) associated protein KLRG1 and increased expression of the memory-precursor effector cell (MPEC) marker CD127 (IL-7Rα).(24) Furthermore, differences were observed in the development of tissue resident memory T-cells (TRM) i…”
Background
A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination
Wieten, R. W., Jonker, E. F. F., van Leeuwen, E. M. M., Remmerswaal, E. B. M., ten Berge, I. J. M., de Visser, A. W., van Genderen, P. J. J., Goorhuis, A., Visser, L. G., Grobusch, M. P., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149871 · Cited by 114 · see citing works
“In this context, high T bet expression fosters the terminal differentiation of functional CD8 T-cells [34, 46, 47] and Eomes is pivotal for sustaining memory subsets [31, 33].”
Background
T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation
Kwong, B., Rua, R., Gao, Y., Flickinger, J. C., Wang, Y., Kruhlak, M. J., Zhu, J., Vivier, É., McGavern, D. B., & Lazarevic, V. (2017) · Nature Immunology · doi:10.1038/ni.3816 · Cited by 114 · see citing works
“T-bet is encoded by Tbx21 and is expressed in multiple immune cell lineages of the immune system 9 .”
Self-citation
Impaired Cytomegalovirus Immunity in Idiopathic Pulmonary Fibrosis Lung Transplant Recipients with Short Telomeres
Popescu, I., Mannem, H. C., Winters, S. A., Hoji, A., Silveira, F. P., McNally, E. J., Pipeling, M. R., Lendermon, E. A., Morrell, M. R., Pilewski, J. M., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201805-0825oc · Cited by 116 · see citing works
Cutting Edge: Eomesodermin Is Sufficient To Direct Type 1 Innate Lymphocyte Development into the Conventional NK Lineage
Pikovskaya, O., Chaix, J., Rothman, N. J., Collins, A., Chen, Y., Scipioni, A. M., Vivier, É., & Reiner, S. L. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502396 · Cited by 111 · see citing works
“1 T cells, and developing Th1 cells (1, 16).”
Background
Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation
Austin, J. W., Buckner, C. M., Kardava, L., Wang, W., Zhang, X., Melson, V. A., Swanson, R. G., Martins, A. J., Zhou, J. Q., Hoehn, K. B., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aax0904 · Cited by 103 · see citing works
“T-bet is best known for its critical role as a transcriptional regulator of several immune lineages, including interferon- (IFN-)–secreting T helper type 1 (TH1) cells (14).”
Background
Singular role for T-BET + CXCR3 + regulatory T cells in protection from autoimmune diabetes
Tan, T. G., Mathis, D. J., & Benoist, C. O. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616710113 · Cited by 103 · see citing works
“CXCR3 induction is dependent on T-BET in Tregs and other leukocyte subsets (10, 11, 33), and both transcripts were overrepresented in insulitic Tregs (Fig.”
Background
The bacterial pathogen Listeria monocytogenes and the interferon family: type I, type II and type III interferons
Dussurget, O., Bierne, H., & Cossart, P. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00050 · Cited by 93 · see citing works
“In NK and NKT cells, the IFN-γ gene locus is transcriptionally permissive within accessible chromatin and allows rapid IFN-γ expression upon activation of transcription factors, such as AP-1, NF-κB, STAT4, and T-bet (Glimcher et al., 2004; Schoenborn and Wilson, 2007; Lazarevic et al., 2013) .”
BackgroundInfluential
Interferon gamma in autoimmunity: A complicated player on a complex stage
Lees, J. R. (2014) · Cytokine · doi:10.1016/j.cyto.2014.10.014 · Cited by 90 · see citing works
“Interestingly, innate capacity to produce IFNc has been described in T and B lymphocyte subsets [27,90] suggesting that cognate antigen driven and non-specific T and B cell activity may both be impacted by locally available IFNc.”
Background
Advances in understanding the pathogenesis of graft‐versus‐host disease
Magenau, J. M., Runaas, L., & Reddy, P. R. (2016) · British Journal of Haematology · doi:10.1111/bjh.13959 · Cited by 90 · see citing works
“Finally, the role of T-bet in regulating DC function is likely to be important for maintaining mucosal homeostasis of the gut, possibly through interactions with host microbiota (Lazarevic et al, 2013).”
Background
The Kynurenine Pathway—New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies
Krupa, A., & Kowalska, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189879 · Cited by 90 · see citing works
Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation
Bam, M., Yang, X., Zumbrun, E. E., Yin, Z., Zhou, J., Ginsberg, J. P., Leyden, Q., Zhang, J., Nagarkatti, P. S., & Nagarkatti, M. (2016) · Scientific Reports · doi:10.1038/srep31209 · Cited by 88 · see citing works
Early enhancer establishment and regulatory locus complexity shape transcriptional programs in hematopoietic differentiation
González, A. J., Setty, M. N., & Leslie, C. S. (2015) · Nature Genetics · doi:10.1038/ng.3402 · Cited by 82 · see citing works
“…previous ChIP-seq studies, including PU.1, RUNX and AP-1 in HSPCs as well as differentiated myeloid and lymphoid cells 27 ; T-BOX/TBET and NF-κ B signals in NK, T cells and monocytes 28 ; myeloid zinc factor MZF in HSPCs and monocytes 29 ; CEBP in monocytes 30 ; and STAT exclusively in T cells 31 .”
Transcriptional and epigenetic networks of helper T and innate lymphoid cells
Shih, H., Sciumè, G., Poholek, A. C., Vahedi, G., Hirahara, K., Villarino, A. V., Bonelli, M. M., Bosselut, R., Kanno, Y., Muljo, S. A., et al. (2014) · Immunological Reviews · doi:10.1111/imr.12208 · Cited by 87 · see citing works
“Even though T-bet (encoded by Tbx21 gene), initially described as a Th1 specific TF (11) and an important factor for acquisition of type 1 features in Th cells, it is also expressed in CD8 T cells, NKT cells, conventional NK cells/ILC1, specific ILC3 subsets, myeloid cells, and B cells (223).”
Background
Optimization of metabolism to improve efficacy during CAR-T cell manufacturing
Zhang, M., Jin, X. K., Sun, R., Xiong, X., Wang, J., Xie, D., & Zhao, M. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-03165-x · Cited by 87 · see citing works
Human T-bet governs the generation of a distinct subset of CD11c high CD21 low B cells
Yang, R., Avery, D. T., Jackson, K., Ogishi, M., Benhsaien, I., Du, L., Ye, X., Han, J., Rosain, J., Peel, J. N., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abq3277 · Cited by 89 · see citing works
A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans
Nellore, A., Zumaquero, E., Scharer, C. D., Fucile, C., Tipton, C. M., King, R. G., Tian, M., Mousseau, B. J., Bradley, J., Zhou, F., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.03.001 · Cited by 87 · see citing works
Expression of the DNA-Binding Factor TOX Promotes the Encephalitogenic Potential of Microbe-Induced Autoreactive CD8+ T Cells
Pagé, N., Klimek, B., Roo, M. D., Steinbach, K., Soldati, H., Lemeille, S., Wagner, I., Kreutzfeldt, M., Liberto, G. D., Vincenti, I., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.04.005 · Cited by 80 · see citing works
“IL-12 is known to inversely regulate the transcription factors Eomes and T-bet, which shape CD8 T cell differentiation (Lazarevic et al., 2013).”
Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells
Lee, P., Yamamoto, T. N., Gurusamy, D., Sukumar, M., Yu, Z., Hu‐Li, J., Kawabe, T., Gangaplara, A., Kishton, R. J., Henning, A. N., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20181218 · Cited by 85 · see citing works
Pathological conditions re-shape physiological Tregs into pathological Tregs
Yang, W. Y., Shao, Y., Lopez‐Pastrana, J., Mai, J., Wang, H., & Yang, X. (2015) · Burns & Trauma · doi:10.1186/s41038-015-0001-0 · Cited by 81 · see citing works
“Similar to T-bet (a T-box gene encoded transcription factor) [14], GATA3 (a trans-acting T cell-specific transcription factor) [15], and RORγt (a RAR-related nuclear orphan receptor family member) [16] identified as the subset-specific transcription factors for the terminal differentiation of type 1 CD4 T helper cells…”
Result
Sustained PI3K Activation exacerbates BLM-induced Lung Fibrosis via activation of pro-inflammatory and pro-fibrotic pathways
Kral-Pointner, J. B., Kuttke, M., Schrottmaier, W. C., Birnecker, B., Warszawska, J. M., Wernig, C., Paar, H., Salzmann, M., Sahin, E., Brunner, J. S., et al. (2016) · Scientific Reports · doi:10.1038/srep23034 · Cited by 81 · see citing works
The paracrine immunomodulatory interactions between the human dental pulp derived mesenchymal stem cells and CD4 T cell subsets
Özdemir, A. T., Özdemir, R. B. Ö., Kırmaz, C., Sarıboyacı, A. E., HALBUTOĞULLARI, Z. S., Özel, C., & Karaöz, E. (2016) · Cellular Immunology · doi:10.1016/j.cellimm.2016.08.008 · Cited by 80 · see citing works
“The expressions of T cell specific cytokines interferon gamma (IFN-g), interleukin (IL)-4 and IL-17a decreased, but IL-10 and transforming growth factor beta-1 (TGF-b1) increased with the hDP-MSCs.”
BackgroundInfluential
Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood-Derived Myeloid Cells in Central Nervous System Inflammation
Wlodarczyk, A., Cédile, O., Jensen, K. N., Jasson, A., Mony, J. T., Khorooshi, R., & Owens, T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00463 · Cited by 88 · see citing works
Hippo Pathway in Mammalian Adaptive Immune System
Yamauchi, T., & Moroishi, T. (2019) · Cells · doi:10.3390/cells8050398 · Cited by 78 · see citing works
“T-bet boosts cytotoxic T cell functions by inducing the effector cytokine IFNγ (interferon gamma) and the cytotoxic protease granzyme B expression [52].”
Background
PD-1 regulation in immune homeostasis and immunotherapy
Gao, M., Shi, J., Xiao, X., Yao, Y., Chen, X., Wang, B., & Zhang, J. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216726 · Cited by 82 · see citing works
mTOR Links Environmental Signals to T Cell Fate Decisions
Chapman, N. M., & Chi, H. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00686 · Cited by 76 · see citing works
“Similarly, these signals drive CD8 T cell differentiation into short-lived effector T cells [SLECs; T-bethiEomesodermin (EOMES)Blimp1hiKLRG1+IL-7Rαlo] or memory precursor cells (MPECs; TbetloEOMESloBlimp-1hiKLRG1loIL-7Rαhi) (80, 81).”
Background
Combination Therapy with NHS-muIL12 and Avelumab (anti-PD-L1) Enhances Antitumor Efficacy in Preclinical Cancer Models
Xu, C., Zhang, Y., Rolfe, A., Hernández, V. M., Guzman, W., Kradjian, G., Marelli, B., Qin, G., Qi, J., Wang, H., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0483 · Cited by 76 · see citing works
“We next examined the effect of combination therapy on the expression of T-bet, a transcription factor involved in several immune functions, including CD8þ T-cell differentiation and cytotoxicity, sustaining memory T-cell subsets, and NK-cell maturation (22, 23).”
Background
M1 Macrophage Derived Exosomes Aggravate Experimental Autoimmune Neuritis via Modulating Th1 Response
Du, T., Yang, C.-L., Ge, M., Liu, Y., Zhang, P., Li, H., Li, X.-L., Li, T., Liu, Y., Dou, Y., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01603 · Cited by 75 · see citing works
“After polarization to M1 phenotypes by combination of IFN-γ from Th1 cells and other environmental changes, macrophages synthesize and release IL-12, which has been considered to be one of the most important environmental clues for Th1 lineage commitment, thus forming a positive feedback and amplifying type 1 immunity…”
Background
The Role of Gut Microbiota-Derived Lithocholic Acid, Deoxycholic Acid and Their Derivatives on the Function and Differentiation of Immune Cells
Kiriyama, Y., & Nochi, H. (2023) · Microorganisms · doi:10.3390/microorganisms11112730 · Cited by 75 · see citing works
“T-bet is considered a master regulator of Th1 cells [75].”
Background
The autoimmune disease-associated transcription factors EOMES and TBX21 are dysregulated in multiple sclerosis and define a molecular subtype of disease
Parnell, G. P., Gatt, P. N., Krupa, M., Nickles, D., McKay, F. C., Schibeci, S. D., Batten, M., Baranzini, S. E., Henderson, A. P. D., Barnett, M. H., et al. (2014) · Clinical Immunology · doi:10.1016/j.clim.2014.01.003 · Cited by 72 · see citing works
“The transcription factors controlling T and NK cell differentiation [12], EOMES and TBX21, were highly dysregulated in untreated MS.”
Background
Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1
DeLong, J. H., Hall, A. O., Konradt, C., Coppock, G., Park, J., Pritchard, G. H., & Hunter, C. A. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701154 · Cited by 69 · see citing works
Dpy30 is critical for maintaining the identity and function of adult hematopoietic stem cells
Yang, Z., Shah, K. K., Khodadadi-Jamayran, A., & Jiang, H. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160185 · Cited by 69 · see citing works
“In addition, a role of Mll4 for cell differentiation in nonhematopoietic systems has also been reported (Lee et al., 2013).”
Background
Intracellular osteopontin regulates homeostasis and function of natural killer cells
Leavenworth, J. W., Verbinnen, B., Wang, Q., Shen, E., & Cantor, H. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1423011112 · Cited by 68 · see citing works
“Because Eomes and T-bet are essential regulators of NK cell homeostasis, maturation and function (7, 22, 23) and phenotypic impairment of OPN-KO NK cells may reflect defective expression of these TFs, we analyzed expression of Eomes and T-bet at the protein level 16 d after NK cell transfer into Rag2γC hosts (Fig.”
Background
Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes
ten Brink, T., Damanik, F., Rotmans, J. I., & Moroni, L. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202301939 · Cited by 71 · see citing works
Complement serves as a switch between CD4+ T cell–independent and –dependent RBC antibody responses
Mener, A., Patel, S. R., Arthur, C. M., Chonat, S., Wieland, A., Santhanakrishnan, M., Liu, J., Maier, C. L., Jajosky, R. P., Girard‐Pierce, K. R., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.121631 · Cited by 67 · see citing works
Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
Tay, R. E., Olawoyin, O. M., Cejas, P., Xie, Y., Meyer, C. A., Ito, Y., Weng, Q. Y., Fisher, D. E., Long, H. W., Brown, M. A., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191453 · Cited by 66 · see citing works
Nod/Ripk2 signaling in dendritic cells activates IL-17A–secreting innate lymphoid cells and drives colitis in T-bet −/− .Rag2 −/− (TRUC) mice
Ermann, J., Staton, T. L., Glickman, J. N., Malefyt, R. D. W., & Glimcher, L. H. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408540111 · Cited by 66 · see citing works
“The transcription factor T-bet controls the differentiation and function of CD4 effector T cells, cytotoxic T cells, and several types of innate immune cells (3).”
BackgroundSelf-citation
T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex
Hertweck, A., Evans, C. M., Eskandarpour, M., Lau, J. C. H., Oļeiņika, K., Jackson, I., Kelly, A., Ambrose, J. C., Adamson, P., Cousins, D. J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.054 · Cited by 65 · see citing works
“T-bet is necessary and sufficient for Th1 cell differentiation (Lazarevic et al., 2013; Szabo et al., 2000).”
BackgroundSelf-citation
Expression Regulation and Function of T-Bet in NK Cells
Huang, C. Y., & Bi, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.761920 · Cited by 61 · see citing works
Arid5a exacerbates IFN-γ–mediated septic shock by stabilizing T-bet mRNA
Zaman, M. M.-U., Masuda, K., Nyati, K. K., Dubey, P. K., Ripley, B., Wang, K., Chalise, J. P., Higa, M., Hanieh, H., & Kishimoto, T. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613307113 · Cited by 64 · see citing works
“T-bet dysregulation has been associated with several Th1-driven immunopathological disorders, suggesting that regulation of T-bet is essential to control the innate immunity (9, 10).”
BackgroundInfluential
Helminth-microbiota cross-talk – A journey through the vertebrate digestive system
Cortés, A., Peachey, L., Scotti, R., Jenkins, T. P., & Cantacessi, C. (2019) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2019.111222 · Cited by 63 · see citing works
“retortaeformisinfected rabbits were positively correlated with levels of expression of T-bet, a key transcription factor defining Th1 cells [54], but not with those of the Treg-related molecules Foxp3 and IL-10 [49] (Fig.”
Adaptive Immunity Against Staphylococcus aureus
Karaüzüm, H., & Datta, S. K. (2016) · Current topics in microbiology and immunology · doi:10.1007/82_2016_1 · Cited by 63 · see citing works
“However, intravenous inoculation of mice deficient in T-bet, which may have deficiencies beyond a defect in Th1 cell IFNγ production (Lazarevic et al. 2013), had increased severity of septic arthritis that was associated with increased weight loss, mortality, and kidney bacterial burden (Hultgren…”
Background
Aging effects on T-bet expression in human B cell subsets
Frasca, D., Diaz, A., Romero, M., D’Eramo, F., & Blomberg, B. B. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.04.007 · Cited by 63 · see citing works
“The transcription factor T-bet, encoded by the Tbx21 gene and originally described as a regulator of Th1 cell differentiation [1,2], has been shown to have a fundamental role also in B cell differentiation and function [1,3–7].”
T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells
Kiekens, L., Loocke, W. V., Taveirne, S., Wahlen, S., Persyn, E., Ammel, E. V., Vos, Z. D., Matthys, P., Nieuwerburgh, F. V., Taghon, T., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.732511 · Cited by 57 · see citing works
NFATc1 Promotes Antitumoral Effector Functions and Memory CD8+ T-cell Differentiation during Non–Small Cell Lung Cancer Development
Heim, L., Friedrich, J., Engelhardt, M., Trufa, D. I., Geppert, C. I., Rieker, R. J., Sı̂rbu, H., & Finotto, S. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3297 · Cited by 61 · see citing works
Antisense targeting of CD47 enhances human cytotoxic T-cell activity and increases survival of mice bearing B16 melanoma when combined with anti-CTLA4 and tumor irradiation
Schwartz, A. L., Nath, P. R., Allgäuer, M., Lessey-Morillon, E. C., Sipes, J. M., Ridnour, L. A., Morillon, Y. M., Yu, Z., Restifo, N. P., & Roberts, D. D. (2019) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-019-02397-7 · Cited by 61 · see citing works
Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction
Lupar, E., Brack, M., Garnier, L., Laffont, S., Rauch, K. S., Schachtrup, K., Arnold, S. J., Guéry, J., & Ízcue, A. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1501159 · Cited by 57 · see citing works
“Although T-bet plays a significant role in CD4 Th responses (20, 56), nonredundant roles of the related transcription factor Eomes on CD4 T cells have not been extensively studied in vivo.”
Background
IL-6 Trans-Signaling Drives Murine Crescentic GN
Braun, G. S., Nagayama, Y., Maruta, Y., Heymann, F., van Roeyen, C. R. C., Klinkhammer, B. M., Boor, P., Villa, L., Salant, D. J., Raffetseder, U., et al. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014111147 · Cited by 58 · see citing works

Authors: Lazarevic, V., Glimcher, L. H., & Lord, G. M.
Affiliations: National Institutes of Health (US)
Weill Cornell Medicine (US)
King's College London (GB)
Corresponding author: Glimcher, Laurie H.
ORCID: Lazarevic, Vanja
Glimcher, Laurie H.
Lord, Graham M.
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2013-10-11
Volume: 13
Issue: 11
Pages: 777-789
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri3536
PMC: PMC6290922
OpenAlex: W2055897422
Cited by: 486
References: 107
Citations by year: 2026: 19 · 2025: 38 · 2024: 26 · 2023: 34 · 2022: 40 · 2021: 41 · 2020: 42 · 2019: 36 · 2018: 50 · 2017: 47 · 2016: 48 · 2015: 32 · 2014: 30 · 2013: 2
FWCI: 3.16
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: Wellcome Trust (WT088747MA)
British Heart Foundation (PG/12/36/29444)
National Institutes of Health
U.S. Public Health Service (P01NSO38037)
Medical Research Council (MR/J006742/1)
National Cancer Institute (R01CA112663, CA112663, ZIABC011431)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: T-bet, transcription factors, innate immunity, adaptive immunity, memory CD8+ T cells, B cells, innate lymphoid cells, dendritic cells, natural killer cells, type 1 immune response, transcriptional regulatory networks, immune cell development
MeSH terms: T-bet Transcription Factor, Animals, B-Lymphocytes, Humans, Immunity, Innate, Immunologic Memory, T-Lymphocyte Subsets, T-Box Domain Proteins, Adaptive Immunity

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T-bet: a bridge between innate and adaptive immunity

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