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

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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

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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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“T-bet transcription factor is expressed in a wide variety of immune cells, including NK cells, NKT cells, B cells, CD4 + and CD8 + T cells, dendritic cells and cd T cells (reviewed by Lazarevic et al , 2013).”
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Background
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Nyati, K. K., & Kishimoto, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.827611 · Cited by 25
“Therefore, disruption of Tbet expression results in various Th1 cells-associated diseases and provides evidence of a role for Tbet regulation in the innate immune response (63, 64).”
Background
Early Expression of Functional Markers on CD4+ T Cells Predicts Outcomes in ICU Patients With Sepsis
Chen, J., Wang, H., Guo, R., Li, H., & Cui, N. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.938538 · Cited by 25
Ibrutinib as an antitumor immunomodulator in patients with refractory chronic lymphocytic leukemia
Cubillos‐Zapata, C., Ortiz, J. A., Córdoba, R., Hernández-Jiménez, E., Toledano, V., de Diego, R. P., & López‐Collazo, E. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1242544 · Cited by 25
“development, between the innate and adaptive immune responses.(9) We observed high T-bet expression on CD4C T cells, suggesting an effect of ibrutinib on CD4C T-cell differentiation (Fig.”
Background
Detection of host pathways universally inhibited after Plasmodium yoelii infection for immune intervention
Xia, L., Wu, J., Pattaradilokrat, S., Tumas, K. C., He, X., Peng, Y., Huang, R., Myers, T. G., Long, C. A., Wang, R., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-33599-1 · Cited by 25
T-bet+ Memory B Cells Link to Local Cross-Reactive IgG upon Human Rhinovirus Infection
Eccles, J. D., Turner, R. B., Kirk, N. A., Muehling, L. M., Borish, L., Steinke, J. W., Payne, S. C., Wright, P. W., Thacker, D. F., Lahtinen, S. J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.027 · Cited by 25
“Although originally defined as a lineage-specifying transcription factor for Th1 cells, T-bet regulates anti-viral B cell responses in mouse models, and is pivotal to B cell differentiation and isotype switching, as well as expression of interferon-γ (IFN-γ) and the chemokine receptor CXCR3 in B cells (Barnett et al.,…”
Background
Mucosal-Associated Invariant T Cells Develop an Innate-Like Transcriptomic Program in Anti-mycobacterial Responses
Sharma, M., Zhang, S., Niu, L., Lewinsohn, D. M., Zhang, X., & Huang, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01136 · Cited by 26
T-cell–restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung
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“T-bet not only promotes the expression of IFN-g, a Th1 cytokine, it also activates CD4(1) T cells while suppressing the type-2 helper, type-17 helper, and T-follicular helper cell differentiation programs, and it is also a critical regulator for controlling antimicrobial type 1 inflammatory responses that coordinate g…”
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Andreev, K., Trufa, I. D. I., Siegemund, R., Rieker, R. J., Hartmann, A., Schmidt, J., Sı̂rbu, H., & Finotto, S. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.255 · Cited by 24
“Some welldescribed anti-tumour effects of IFN-g are upregulation of MHC *Correspondence: Professor S Finotto; E-mail: susetta.finotto@uk-erlangen.de 5These two authors share the first authorship Revised 6 May 2015; accepted 4 June 2015; published online 8 September 2015 & 2015 Cancer Research UK.”
Background
RSK2 phosphorylates T-bet to attenuate colon cancer metastasis and growth
Yao, K., Peng, C., Zhang, Y., Zykova, T. A., Lee, M., Lee, S., Rao, E., Chen, H., Ryu, J., Wang, L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710756114 · Cited by 24
“T-bet undergoes posttranslational protein modifications and can determine cell fate by exerting direct stimulatory or indirect inhibitory activity on target gene expression (12).”
Background
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Avery, D., Morandini, L., Gabriec, M., Sheakley, L. S., Peralta, M. M., Donahue, H. J., Martin, R., & Olivares‐Navarrete, R. (2023) · Acta Biomaterialia · doi:10.1016/j.actbio.2023.07.052 · Cited by 24
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“restimulation (38, 39) and is triggered by inflammatory signals (40).”
Background
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Raju, S., Kometani, K., Kurosaki, T., Shaw, A. S., & Egawa, T. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007053 · Cited by 25
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“An array of immune cells other than helper T cells also express Tbet, including dendritic cells (DC), CD8+ T cells, Innate Lymphoid Cells, Natural Killer cells, Natural Killer T cells and γδT cells [31].”
Background
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“transcription factors are T-bet for Th1 cell lineage, and GATA3 for Th2 cell lineage.((24)) Consistent with its effects on serum IL-4 and IFN-γ levels, A-AHT treatment signifi cantly increased T-bet expression and T-bet/GATA3 ratio compared with the AD model mice.”
Result
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“T-bet directly induces CD122 (IL-15Rβ) transcription and subsequently promotes iNKT cell survival [49].”
Background
Existence and stability of periodic solutions of an impulsive differential equation and application to CD8 T-cell differentiation
Girel, S., & Fabien Crauste, A. (2018) · Journal of Mathematical Biology · doi:10.1007/s00285-018-1220-3 · Cited by 23
“…the emergence of two subpopulations of effector CD8 T-cells, with the first ones—characterised by a low level of Tbet—able to develop memory properties and the second ones—characterised by a high level of Tbet—destined to die during the contraction phase (Kaech and Cui 2012; Lazarevic et al. 2013).”
BackgroundInfluential
Reactive glia promote development of CD103+CD69+ CD8+ T‐cells through programmed cell death‐ligand 1 (PD‐L1)
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“Previous studies have implicated involvement of the transcription factors T-bet and Eomes in acquisition of CD8þ T-cell effector function and the development of memory CD8þ T-cells [15, 27, 43].”
Background
TYK2 signaling promotes the development of autoreactive CD8+ cytotoxic T lymphocytes and type 1 diabetes
Mine, K., Nagafuchi, S., Akazawa, S., Abiru, N., Mori, H., Kurisaki, H., Shimoda, K., Yoshikai, Y., Takahashi, K., & Anzai, K. (2024) · Nature Communications · doi:10.1038/s41467-024-45573-9 · Cited by 22
“A previous study reported Cxcr3 , a receptor for CXCL9 and CXCL10, is a target gene of T-BET 48 .”
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Milotay, G., Little, M., Watson, R. A., Muldoon, D., MacKay, S., Kurioka, A., Tong, O., Taylor, C. A., Nassiri, I., Webb, L. M., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03647-1 · Cited by 23
“41), further corroborating cICB-specific induction of cytotoxic responses in CMV − patients.”
T‐bet transcription factor in cardiovascular disease: Attenuation or inflammation factor?
Haybar, H., Rezaeeyan, H., Shahjahani, M., Shirzad, R., & Saki, N. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27935 · Cited by 22
Susceptibility Factors in Chronic Lung Inflammatory Responses to Engineered Nanomaterials
You, D. J., & Bonner, J. C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197310 · Cited by 24
“T-box transcription factor TBX21 (T-bet) is a transcription factor that plays a critical role in the development and differentiation of TH1 cells in the lung [85].”
Background
Mumps virus-specific immune response outcomes and sex-based differences in a cohort of healthy adolescents
Riggenbach, M. M., Haralambieva, I. H., Ovsyannikova, I. G., Schaid, D. J., Poland, G. A., & Kennedy, R. B. (2021) · Clinical Immunology · doi:10.1016/j.clim.2021.108912 · Cited by 22
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Le, T., Reeves, R. K., & McKinnon, L. R. (2022) · Immunology · doi:10.1111/imm.13523 · Cited by 23
“These transcription factors are also involved in the development of memory T cells, which suggests possible shared mechanisms in their induction of adaptive NK cells [45, 46].”
Background
Synergy between Th1 and Th2 responses during endometriosis: A review of current understanding
Chang, L.-Y., Shan, J., Hou, X., Li, D., & Wang, X.-Q. (2023) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2023.103975 · Cited by 24
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Targeting the T-Cell Lymphoma Epigenome Induces Cell Death, Cancer Testes Antigens, Immune-Modulatory Signaling Pathways
Scotto, L., Kinahan, C., Douglass, E. F., Deng, C., Safari, M., Casadei, B., Marchi, E., Lue, J. K., Montanari, F., Falchi, L., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0377 · Cited by 21
“In concert with STAT4, TBX21 (T-bet) has been shown to play a central role in the generation of transcriptionally competent TH1 cellspecific genes in CD4-positive T cells (30).”
Background
Interferon-γ signal drives differentiation of T-bethi atypical memory B cells into plasma cells following Plasmodium vivax infection
Kochayoo, P., Thawornpan, P., Wangriatisak, K., Changrob, S., Leepiyasakulchai, C., Khowawisetsut, L., Adams, J. H., & Chootong, P. (2022) · Scientific Reports · doi:10.1038/s41598-022-08976-6 · Cited by 21
Transcriptional and Epigenetic Regulation of Context-Dependent Plasticity in T-Helper Lineages
Friedman, M. J., Lee, H., Lee, J., & Oh, S. (2023) · Immune Network · doi:10.4110/in.2023.23.e5 · Cited by 22
“Along with STAT4-dependent activation of the Th1-specific enhancer landscape (50), T-bet activates most of the Th1 cell-specific genes, including cytokines, chemokines, and chemokine receptors, that are required for the function of Th1 cells (51).”
Background
A novel lineage transcription factor based analysis reveals differences in T helper cell subpopulation development in infected and intrauterine growth restricted (IUGR) piglets
Ebner, F., Rausch, S., Scharek‐Tedin, L., Pieper, R., Burwinkel, M., Zentek, J., & Hartmann, S. (2014) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2014.05.005 · Cited by 21
B-cell abnormalities in HIV-1 infection
Kardava, L., & Moir, S. L. (2019) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000547 · Cited by 21
“T-bet, master regulator of T helper 1 (Th1) lineage commitment, also regulates immunoglobulin class-switching, preferentially IgG2a/c in mice and IgG1 and IgG3 in humans, under IFN-g-dependent conditions [24].”
Background
The role of mitochondrial transfer in the suppression of CD8+ T cell responses by Mesenchymal stem cells
Vaillant, L., Akhter, W., Nakhle, J., Simon, M., Villalba, M., Jørgensen, C., Vignais, M., & Hernández, J. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03980-1 · Cited by 23
“Since T-bet expression is triggered by TCR signaling and also dependent on mTORC1 activity [64], it is likely that mitochondrial uptake by CD8 + and Th1 cells is interfering with the IP3-AKT-mTOR pathway.”
BackgroundInfluential
T-bet+ Cells Polarization in Patients Infected with Helicobacter pylori Increase the Risk of Peptic Ulcer Development
Bagheri, N., Shirzad, H., Mirzaei, Y., Nahid‐Samiei, M., Sanaei, M., Rahimian, G., Shafigh, M., Zandi, F., Tahmasbi, K., & Razavi, A. (2019) · Archives of Medical Research · doi:10.1016/j.arcmed.2019.07.005 · Cited by 20
The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies
McKay, F. C., Gatt, P. N., Fewings, N., Parnell, G. P., Schibeci, S. D., Basuki, M. A., Powell, J. E., Goldinger, A., Fabis‐Pedrini, M. J., Kermode, A. G., et al. (2016) · Clinical Immunology · doi:10.1016/j.clim.2015.12.015 · Cited by 20
“ETlow, is defined by lower expression of the genes EOMES encoding eomesodermin (also known as T-box brain 2) and TBX21 encoding T-bet (T-box expressed in T cells; highly homologous to Eomes), transcription factors that control NK/CD8 memory and CD4 differentiation [15].”
Background
Immune response in the adipose tissue of lean mice infected with the protozoan parasite Neospora caninum
Teixeira, L., Moreira, J., Melo, J., Bezerra, F., Marques, R. M., Ferreirinha, P., Correia, A., Monteiro, M. P., Ferreira, P. G., & Vilanova, M. (2015) · Immunology · doi:10.1111/imm.12440 · Cited by 21
Role of TGF-β in anti-rhinovirus immune responses in asthmatic patients
Bielor, C., Sopel, N., Maier, A., Blau, A., Sharma, H., Vuorinen, T., Kroß, B., Mittler, S., Graser, A., Mousset, S., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.10.049 · Cited by 20
Epigenetic and Genetic Regulation of PDCD1 Gene in Cancer Immunology
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Alterations in T-Cell Transcription Factors and Cytokine Gene Expression in Late-Onset Alzheimer’s Disease
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“The transcription factor T-bet, encoded by the Tbx21 gene, is the Th1 cell-deﬁning transcription factor [67, 68].”
CTLA-4 expressing innate lymphoid cells modulate mucosal homeostasis in a microbiota dependent manner
Lo, J. W., Schroeder, J.-H., Beattie, G., Roberts, L. B., Cozzetto, D., Omer, O., Ross, E. M., Heuts, F. W. H., Jowett, G. M., Read, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51719-6 · Cited by 21
Self-citation
Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia
Landry, J., Martinov, T., Mengistu, H., Dhanwada, J., Benck, C. J., Kline, J. M., Boo, B., Swanson, L., Tonc, E., Daughters, R. S., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169672 · Cited by 19
Exposure of Human CD8+ T Cells to Type-2 Cytokines Impairs Division and Differentiation and Induces Limited Polarization
Fox, A., Harland, K. L., Kedzierska, K., & Kelso, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01141 · Cited by 18
Immunomodulatory asthma therapy in the equine animal model: A dose‐response study and evaluation of a long‐term effect
Klier, J., Bartl, C., Geuder, S., Geh, K. J., Reese, S., Goehring, L. S., Winter, G., & Gehlen, H. (2019) · Immunity Inflammation and Disease · doi:10.1002/iid3.252 · Cited by 21
“In addition, it influences both the acquired immune system, as well as the innate immune system.(78) The CpGsd showed a reduction of the T‐bet expression after 8 weeks.”
Background
Coordinated immune dysregulation in juvenile dermatomyositis revealed by single-cell genomics
Rabadam, G., Wibrand, C., Flynn, E., Hartoularos, G. C., Sun, Y., Madubata, C. J., Fragiadakis, G. K., Ye, C., Kim, S., Gartner, Z. J., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.176963 · Cited by 21
Emerging point‐of‐care autologous cellular therapy using adipose‐derived stromal vascular fraction for neurodegenerative diseases
Al‐kharboosh, R., Perera, J., Bechtle, A. R., Bu, G., & Quiñones‐Hinojosa, A. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.1093 · Cited by 20
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Wu, K. Y., Kulbay, M., Daigle, P., Nguyen, B. H., & Tran, S. D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031553 · Cited by 20
“Given that T-bet is a key regulator of T cell differentiation and that the expression of miR-29a-3p was shown to be increased in patients with NSOI, its specific role in inflammation and autoimmunity in this disease remains to be elicited [106].”
Background
Lkb1 orchestrates γδ T-cell metabolic and functional fitness to control IL-17-mediated autoimmune hepatitis
Xiao, Z., Wang, S., Luo, L., Lv, W., Feng, P., Sun, Y., Yang, Q., He, J., Cao, G., Yin, Z., et al. (2024) · Cellular and Molecular Immunology · doi:10.1038/s41423-024-01163-9 · Cited by 20
Eomesodermin driven IL-10 production in effector CD8+ T cells promotes a memory phenotype
Reiser, J., Sadashivaiah, K., Furusawa, A., Banerjee, A., & Singh, N. J. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2018.11.008 · Cited by 20
“It is well established that higher Eomes levels favor the maintenance of a functional CD8+ memory T cell population (1, 7, 11, 13, 14).”
Background
Increased Expression of T-Box Transcription Factor Protein 21 (TBX21) in Skin Cutaneous Melanoma Predicts Better Prognosis: A Study Based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) Databases
Zhang, X., Wen, X., Feng, N., Chen, A., Yao, S., Ding, X., & Zhang, L. (2020) · Medical Science Monitor · doi:10.12659/msm.923087 · Cited by 18
“T-bet regulates the balance of Th1/Th2 cells [10].”
Background
Antiviral memory B cells exhibit enhanced innate immune response facilitated by epigenetic memory
Zhu, X., Hong, S., Bu, J., Liu, Y., Liu, C., Li, R., Zhang, T., Zhang, Z., Li, L., Zhou, X., et al. (2024) · Science Advances · doi:10.1126/sciadv.adk0858 · Cited by 19
Context-dependent T-BOX transcription factor family: from biology to targeted therapy
Li, S., Luo, X., Sun, M., Wang, Y., Zhang, Z., Jiang, J., Hu, D., Zhang, J., Wu, Z., Wang, Y., et al. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01719-2 · Cited by 18
“…activation (via IFNγ, STAT1, and IL-12R), trafficking (via C-C motif chemokine ligand 3 [CCL3], C-X-C motif chemokine receptor 3 [CXCR3], tyrosine-protein sulfotransferase 2 [TPST2], and CD11a), and immune regulation (via IL-2, IL-4, IL-5, and RAR-related orphan receptor-γ [RORγt]) [147, 148].”
Background
Transcriptional regulation of T cell metabolism
Hough, K. P., Chisolm, D. A., & Weinmann, A. S. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2015.07.038 · Cited by 19
CD8+IL-17+ T Cells Mediate Neutrophilic Airway Obliteration in T-bet–Deficient Mouse Lung Allograft Recipients
Lendermon, E. A., Dodd‐o, J. M., Coon, T. A., Miller, H. L., Ganguly, S., Popescu, I., O'Donnell, C. P., Cárdenes, N., Levine, M., Rojas, M. M., et al. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2014-0059oc · Cited by 17
T‐bet as a key regulator of mucosal immunity
Mohamed, R., & Lord, G. M. (2016) · Immunology · doi:10.1111/imm.12575 · Cited by 17
Self-citation
Circulating Memory B Cells in Early Multiple Sclerosis Exhibit Increased IgA+ Cells, Globally Decreased BAFF-R Expression and an EBV-Related IgM+ Cell Signature
Leffler, J., Trend, S., Ward, N. C., Grau, G. E., Hawke, S. H., Byrne, S. N., Kermode, A. G., French, M. A., & Hart, P. H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.812317 · Cited by 17
Clinical significance of T-bet, GATA-3, and Bcl-6 transcription factor expression in bladder carcinoma
Bahria-Sediki, I. B., Yousfi, N., Paul, C., Chébil, M., Chérif, M., Zermani, R., Gaaied, A. B. A. E., & Bettaı̈eb, A. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-0891-z · Cited by 17
“Although T-bet is the master regulator of Th1 cell differentiation, it is expressed in multiple cells of the innate and adaptive immune system, including innate lymphoid cells (ILCs) [4, 5].”
Background
Yeast cell wall upregulated cell-mediated immune responses to Newcastle disease virus vaccine
Bi, S., Zhang, J., Zhang, L., Huang, K. G., Li, J., & Cao, L. (2022) · Poultry Science · doi:10.1016/j.psj.2022.101712 · Cited by 16
“In this study, both T-bet and GATA-3 in spleen were upregulated in broilers treated with YP and vaccine, indicating that a balanced Th1/Th2 response was induced by YP.”
Influential
Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling
Zheng, H., Wang, X., He, X., Chen, M., Zhang, M., Lian, X., Song, J., Hu, Y., Pang, W., Wang, Y., et al. (2022) · Cellular and Molecular Immunology · doi:10.1038/s41423-022-00899-6 · Cited by 15
Roles for Helper T Cell Lineage-Specifying Transcription Factors in Cellular Specialization
Weinmann, A. S. (2014) · Advances in immunology · doi:10.1016/b978-0-12-800147-9.00006-6 · Cited by 16
Eomesodermin promotes interferon‐γ expression and binds to multiple conserved noncoding sequences across the Ifng locus in mouse thymoma cell lines
Fukuoka, N., Harada, M., Nishida, A., Ito, Y., Shiota, H., & Kataoka, T. (2016) · Genes to Cells · doi:10.1111/gtc.12328 · Cited by 16
“Epigenetic control by multiple transcription factors plays an essential role in the lineage-specific expression of IFN-c (Wilson et al. 2009; Miller & Weinmann 2010; Aune et al. 2013; Lazarevic et al. 2013).”
BackgroundInfluential
Tasquinimod modulates tumor-infiltrating myeloid cells and improves the antitumor immune response to PD-L1 blockade in bladder cancer
Nakhlé, J., Pierron, V., Bauchet, A.-L., Plas, P., Thiongane, A., Meyer-Losic, F., & Schmidlin, F. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1145333 · Cited by 16
“differentiation of naive T cells into Th1 cells.(28) It is also a potent inducer of IFNg production.”
Background
T-box transcription factor 21 expression in breast cancer and its relationship with prognosis.
Yu, H., Yang, J., Jiao, S., Li, Y., Zhang, W., & Wang, J. (2014) · PubMed Central · Cited by 16
Molecular and cellular bases of trained immunity
Sun, S. J., Aguirre‐Gamboa, R., & Barreiro, L. B. (2026) · Immunity · doi:10.1016/j.immuni.2026.03.001 · Cited by 18
Emerging interleukin targets in the tumour microenvironment: implications for the treatment of gastrointestinal tumours
Dickerson, L. K., Carter, J. A., Kohli, K., & Pillarisetty, V. G. (2023) · Gut · doi:10.1136/gutjnl-2023-329650 · Cited by 17
Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease
Balakrishnan, A., Gloude, N. J., Šášik, R., Ball, E. D., & Morris, G. P. (2017) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2017.07.016 · Cited by 15
“CD4+ (RUNX1+) and CD8+ (RUNX1−) dual TCR T cells from patients with cGVHD (Figure 6A) demonstrated frequent expression of TBX21 (Tbet), a promoting factor for proinflammatory Th1 CD4+ and cytotoxic CD8+ T cell function [36].”
Background
Incorporating mucosal-associated invariant T cells into the pathogenesis of chronic liver disease
Czaja, A. J. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i25.3705 · Cited by 16
spv locus aggravates Salmonella infection of zebrafish adult by inducing Th1/Th2 shift to Th2 polarization
Wu, S., Wang, L.-D., Xu, G.-M., Yang, S., Deng, Q., Li, Y., & Huang, R. (2017) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2017.06.057 · Cited by 15
“GATA-3 is known to be a key regulator of Th2 development and influences the expression of Th2 cytokines such as IL-4, IL-10, and IL-13 etc [6,7].”
Background
T-Helper 1 Immune Response in Metastatic Lymph Nodes of Pancreatic Ductal Adenocarcinoma: A Marker For Prolonged Survival
Nizri‏, E., Sternbach, N., Bar-David, S., Yehuda, A. B., Gerstenhaber, F., Dovrat, T. O., Wolf, I., Weiner, G., Lahat, G., & Klausner, J. M. (2017) · Annals of Surgical Oncology · doi:10.1245/s10434-017-6237-0 · Cited by 15
Tumor microenvironment dynamics in gastric cancer pathogenesis and therapeutic resistance
Lu, Z., Zhang, Q., Han, J., Ji, J., & Xing, X. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02572-2 · Cited by 16
T-bet+CD8+ T cells govern anti-PD-1 responses in microsatellite-stable gastric cancers
Tang, S., Che, X., Wang, J., Li, C., He, X., Hou, K., Zhang, X., Guo, J., Yang, B., Li, D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58958-1 · Cited by 13
“Original data was generated by ﬂ ow cytometer analysis. j Box plots of geometric mean ﬂ uorophore intensities (gMFIs) of IFN-γ ( P =7.685e-04, two-tailed Mann-Whitney U test) and GZMB ( P =2.461e-04, two-tailed Mann-Whitney U test) in T-bet + CD8 + T cells and T-bet - CD8 + T cells from 10 CDX GC tumors. k Kaplan-Meie…”
Influential
Variations in T Cell Transcription Factor Sequence and Expression Associated with Resistance to the Sheep Nematode Teladorsagia circumcincta
Wilkie, H., Gossner, A. G., Bishop, S. C., & Hopkins, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149644 · Cited by 14
“T-bet ( TBX21 ) promotes Th1 differentiation by transactivating IFNG and increasing IFN γ production, and by repressing Th2 activation [22, 23].”
Heat stress, Eimeria spp. and C. perfringens infections alone or in combination modify gut Th1/Th2 cytokine balance and avian necrotic enteritis pathogenesis
Calefi, A. S., Quinteiro-Filho, W. M., de Siqueira, A., Lima, A. P., da Cruz, D. S. G., Hazarbassanov, N. Q., Salvagni, F. A., Borsoi, A., Massoco, C. D. O., Maiorka, P. C., et al. (2019) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2019.03.001 · Cited by 14
“Several models have been proposed to experimentally reproduce this disease in chickens as it occurs in the field (Lee et al., 2011).”
Background
Adverse prognostic impact of regulatory T‐cells in testicular diffuse large B‐cell lymphoma
Pollari, M., Pellinen, T. S., Karjalainen‐Lindsberg, M., Kellokumpu‐Lehtinen, P., Leivonen, S., & Leppä, S. (2020) · European Journal Of Haematology · doi:10.1111/ejh.13484 · Cited by 14
miR-155 regulates pro- and anti-inflammatory cytokine expression in human monocytes during chronic hepatitis C virus infection
Zhou, Y., Zhang, P., Zheng, X., Ye, C., Li, M., Bian, P., Fan, C., & Zhang, Y. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-2620 · Cited by 14
“In the absence of T-bet, DCs are unable to efficiently prime Th1 cell responses (9).”
Activation of T-bet, FOXP3, and EOMES in Target Organs From Piglets Infected With the Virulent PRRSV-1 Lena Strain
Ruedas‐Torres, I., Gómez-Laguna, J., Sánchez‐Carvajal, J. M., Larenas‐Muñoz, F., Barranco, I., Pallarés, F. J., Carrasco, L., & Rodríguez-Gómez, I. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.773146 · Cited by 14
Developing effective vaccines: Cues from natural infection
Bhurani, V., Mohankrishnan, A., Morrot, A., & Dalai, S. K. (2018) · International Reviews of Immunology · doi:10.1080/08830185.2018.1471479 · Cited by 17
Multi-Dimensional Gene Regulation in Innate and Adaptive Lymphocytes: A View From Regulomes
Fernando, N., Sciumè, G., O’Shea, J. J., & Shih, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.655590 · Cited by 14
“T-bet expression is exclusively essential for both lineage specification and function in ILC1 and Th1 cells, as these lymphocytes do not express EOMES (32, 33).”
BackgroundInfluential
Enhancing thymic function improves T-cell reconstitution and immune responses in aged mice
Morales‐Sánchez, A., Lavaert, M., Vacchio, M. S., Martinez‐Ruíz, G. U., Egbase, D., Zhao, Y., Lake, R. G., Ishikawa, M., Braikia, F.-Z., Jankovic, D. L., et al. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003283 · Cited by 13
Petroleum extract of Farfarae Flos alleviates nasal symptoms by regulating the Th1-Th2 cytokine balance in a mouse model of Allergic Rhinitis
Wu, Y., Zhao, X., Cui, J., Guo, Y., Zheng, X., Zhang, Y., Niu, M., Li, Z., Wen, S., & Gao, W. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.52915 · Cited by 14
“T-bet, a member of the t-box gene family; is selectively expressed in Th1 cells, where it not only promotes Th1 cell differentiation and IFN-γ secretion but also inhibits GATA3 expression and influences IL-4 signaling and Th2 cell differentiation [35].”
Background
Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory Precursors
Neitzke‐Montinelli, V., Calôba, C., Melo, G. A., Frade, B. B., Caramez, E., Mazzoccoli, L., Gonçalves, A. N. A., Nakaya, H. I., Pereira, R. M., Werneck, M. B. F., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.840203 · Cited by 13
TBX 21 participates in innate immune response by regulating Toll‐like receptor 2 expression in S treptococcus pneumoniae infections
Woo, C.-H., Shin, S. G., Koh, S. H., & Lim, J. H. (2014) · Molecular Oral Microbiology · doi:10.1111/omi.12061 · Cited by 13
Immunomodulatory effect of psoriasis-derived dermal mesenchymal stem cells on TH1/TH17 cells
Zhao, X., Jiao, J., Li, X., Hou, R., Li, J., Niu, X., Liu, R., Yang, X., Li, J., Liang, J., et al. (2021) · European Journal of Dermatology · doi:10.1684/ejd.2021.4050 · Cited by 13
Iron Prevents the Development of Experimental Cerebral Malaria by Attenuating CXCR3-Mediated T Cell Chemotaxis
Ham, K. M. V. D., Shio, M. T., Rainone, A., Fournier, S., Krawczyk, C. M., & Olivier, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118451 · Cited by 13
“IFNγ signalling through the IFNγR (IFNγR1/IFNγR2) induces T-bet, which subsequently transactivates both IFNγ and CXCR3 [40].”
Background
Biology of peripheral T cell lymphomas – Not otherwise specified: Is something finally happening?
Maura, F., Dodero, A., Carniti, C., & Bolli, N. (2016) · Pathogenesis · doi:10.1016/j.pathog.2016.02.002 · Cited by 13
“3) [72].”
Deoxynivalenol Has the Capacity to Increase Transcription Factor Expression and Cytokine Production in Porcine T Cells
Vatzia, E., Pierron, A., Hoog, A., Saalmüller, A., Mayer, E., & Gerner, W. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02009 · Cited by 12
Resistance mechanisms to programmed cell death protein 1 and programmed death ligand 1 inhibitors
Pezeshki, P. S., Sharif, P. M., & Rezaei, N. (2021) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2021.1929919 · Cited by 13
NHS-IL12 and bintrafusp alfa combination therapy enhances antitumor activity in preclinical cancer models
Xu, C., Marelli, B., Qi, J., Qin, G., Yu, H., Wang, H., Jenkins, M. H., Lo, K.-M., & Lan, Y. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101322 · Cited by 12
Association of T-Bet, GATA-3, RORC, and FOXP3 Copy Number Variations With Acute Anterior Uveitis With or Without Ankylosing Spondylitis in Chinese Han
Bai, L., Liu, Y., Hou, S., Liao, D. K., Kijlstra, A., & Yang, P. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-17960 · Cited by 12
TBX21 attenuates colorectal cancer progression via an ARHGAP29/RSK/GSK3β dependent manner
Jiang, X., Du, W., Yang, C., Wang, S., Li, Y., Shen, X., Yang, X., Yao, J., Du, R., Zhang, X., et al. (2023) · Cellular Oncology · doi:10.1007/s13402-023-00809-6 · Cited by 11
“TBX21 is a member of the T-box family of transcription factors that coordinates the differentiation and function of multiple immune system cells [ 31 ].”
Background
Innate lymphoid cells, immune functional dynamics, epithelial parallels, and therapeutic frontiers in infections
Nouari, W., & Aribi, M. (2025) · International Reviews of Immunology · doi:10.1080/08830185.2025.2490233 · Cited by 11
Distinct association between chronic Epstein-Barr virus infection and T cell compartments from pediatric heart, kidney, and liver transplant recipients
Yamada, M., Macedo, C., Louis, K., Shi, T., Landsittel, D. P., Nguyen, C., Shinjoh, M., Michaels, M. G., Feingold, B., Mazariegos, G. V., et al. (2023) · American Journal of Transplantation · doi:10.1016/j.ajt.2023.05.007 · Cited by 11
The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice
Scott, O., Visuvanathan, S., Reddy, E. C., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1183273 · Cited by 12
Density-dependent effects of Caligus rogercresseyi infestation on the immune responses of Salmo salar
Boltaña, S., Sanchez, M., Valenzuela, V., & Gallardo‐Escárate, C. (2016) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2016.11.002 · Cited by 11
Most Variable Genes and Transcription Factors in Acute Lymphoblastic Leukemia Patients
Tomar, A. K., Agarwal, R., & Kundu, B. (2019) · Interdisciplinary Sciences Computational Life Sciences · doi:10.1007/s12539-019-00325-y · Cited by 11
Immune predictors of mortality following RNA virus infection
Graham, J. B., Swarts, J. L., Menachery, V. D., Gralinski, L. E., Schäfer, A., Plante, K. S., Morrison, C. R., Voss, K., Green, R. R., Choonoo, G., et al. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiz531 · Cited by 12
“Building from these findings, we next assessed the frequency of baseline splenic T cells that expressed the transcription factor Tbet, which indicates a Th1 phenotype linked with secretion of interferon (IFN)γ, known to be a potent antiviral cytokine [21] .”
Background
Topical exposure to triclosan inhibits Th1 immune responses and reduces T cells responding to influenza infection in mice
Shane, H. L., Othumpangat, S., Marshall, N. B., Blachère, F. M., Lukomska, E., Weatherly, L. M., Baur, R., Noti, J. D., & Anderson, S. E. (2020) · PLoS ONE · doi:10.1371/journal.pone.0244436 · Cited by 10
“Some of these cytokines (IL-5, IL-13, IFN-γ and IL-10) were significantly upregulated only in the VC/PR8 group and not the TCS/PR8 group.”
Background

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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