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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Background
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Background
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Background
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Background
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Background
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“…expression is irreversibly associated with Th1 differentiation and is important for the terminal differentiation of memory CD4 + and CD8 + T cells during acute infections and for preventing CD8 + T cell exhaustion during chronic antigen stimulation [23,24] (Figure 1). towards other Th subsets [23].”
Background
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BackgroundInfluential
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Background
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Background
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Background
OCH Ameliorates Bone Marrow Failure in Mice via Downregulation of T-Bet Expression
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“T-bet is a recently identified transcription factor belonging to T-box family [5].”
Background
Global deletion of the immune cell transcription factor, T-bet, alters gut microbiota and insulin sensitivity in mice
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“A known critical transcriptional factor in T cell function, this suggested an important role for methylation of TBX21 in CRC [24].”
Background
Hematopoietic PI3Kδ deficiency aggravates murine atherosclerosis through impairment of Tregs
Zierden, M., Berghausen, E. M., Gnatzy-Feik, L., Millarg, C., Picard, F. S. R., Kiljan, M., Geißen, S., Polykratis, A., Zimmermann, L., Nies, R. J., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.155626 · Cited by 5
“However, these findings do not necessarily indicate a restored Th1 response as these markers are principally expressed by multiple subsets of immune and nonimmune cells (45).”
Background
Eomesodermin promotes interaction of RelA and NFATc2 with the Ifng promoter and multiple conserved noncoding sequences across the Ifng locus in mouse lymphoma BW5147 cells
Harada, M., Nghia, V. T., Nakao, A., Tanigaki, R., Fukuoka, N., Nishida, A., & Kataoka, T. (2020) · Immunology Letters · doi:10.1016/j.imlet.2020.06.008 · Cited by 4
Repeated dermal application of the common preservative methylisothiazolinone triggers local inflammation, T cell influx, and prolonged mast cell-dependent tactile sensitivity in mice
Kline, J. M., Arriaga-Gomez, E. A., Tenzin, Y., Boo, B., Landry, J., Saldías-Montivero, M., Neamonitaki, N., Mengistu, H., Silverio, S., Zacheis, H., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0241218 · Cited by 4
“Additionally, transcripts encoding Tbx21, an important driver of IFN-γ production [26], were increased by an average of 1.”
Background
Innate lymphoid cell subsets and their cytokines in autoimmune diseases
Maleki, A., Khanmiri, J. M., Khani-Eshratabadi, M., Soveyzi, F., Moazzami, B., Hamblin, M. R., & Rezaei, N. (2020) · European Cytokine Network · doi:10.1684/ecn.2020.0460 · Cited by 4
“The T-box transcription factor 21 (Tbx21) encodes the immune cell transcription factor called T-bet that controls the growth of TH1 cells [52].”
Background
Type 3 immune response protects against Salmonella Typhimurium infection in the small intestine of neonatal rats
Yang, Z., Zhang, M., Gao, N., Peng, J., & Wei, H. (2024) · Emerging Microbes & Infections · doi:10.1080/22221751.2024.2417867 · Cited by 3
“Type 1 immune cells, driven by the transcription factor T-bet and producing cytokines like IFN-γ, are essential for controlling intra-cellular pathogens [7].”
Background
Preexisting vaccine-primed heterosubtypic T cell immunity protects the maternal-fetal unit from adverse influenza outcomes in mice
Flores-Malavet, V., Dhume, K., Satchmei, A., Arvelo, A. C., Beaird, A. J., Annamalai, S. N., Kimball, L. A., McKinstry, K. K., & Strutt, T. M. (2025) · Journal of Clinical Investigation · doi:10.1172/jci179230 · Cited by 3
Epigenomic control of immunity: from mechanisms to therapeutic targets in inflammatory bowel diseases
Shih, H., Sciumè, G., & Mikami, Y. (2025) · International Immunology · doi:10.1093/intimm/dxaf039 · Cited by 3
“For instance, lineage-determining transcription factors in NK cells, such as T-bet, establish primed enhancer landscapes critical for subsequent immune responses (78).”
Feeder-free advances in T cell development and therapy
Zhu, E., Liu, Z., & Li, Y.-R. (2025) · Cell Biomaterials · doi:10.1016/j.celbio.2025.100244 · Cited by 3
Systematic discovery of pro- and anti-HIV host factors in primary human CD4+ T cells
Rathore, U., Dugan, E. J., Thornton, H., Kumar, V. E., Dajani, R., Burdick, R. C., Young, J. M., Steinhart, Z., Lao, R., Delviks‐Frankenberry, K. A., et al. (2026) · Cell · doi:10.1016/j.cell.2026.03.046 · Cited by 4
Isoprinosine as a foot-and-mouth disease vaccine adjuvant elicits robust host defense against viral infection through immunomodulation
Kim, H. W., Ko, M.-K., Shin, S., Park, S. H., Park, J.-H., Kim, S.-M., & Lee, M. J. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1331779 · Cited by 3
Patient-Specific Regulatory Network Rewiring in Inflammatory Bowel Disease: How Genetic Polymorphisms Divert Incoming Signals and Contribute to Disease Pathogenesis
Bohár, B., Thomas, J. P., Liu, Y., Brooks-Warburton, J., Verstockt, B., Powell, N., Korcsmáros, T., & Módos, D. (2025) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izaf173 · Cited by 3
Expression analysis of IL-2, TBX21 and SOCS1 in peripheral blood cells of celiac disease patients reveals the diagnostic potential of IL-2
Ganjali, F., Asri, N., Rostami‐Nejad, M., Hashemi, M., Ainy, E., Masotti, A., & Aghdaei, H. A. (2023) · Molecular Biology Reports · doi:10.1007/s11033-023-08394-5 · Cited by 3
Co-expression gene module analysis in response to attenuated cercaria vaccine reveals a critical role for NK cells in protection against Schistosoma mansoni
Neto, A. P. D. S., Vitoriano-Souza, J., Khouri, M. I., Fávaro, R. D., Wilson, R. A., Leite, L. C. C., Ramos, P. I. P., & Farias, L. P. (2024) · Parasites & Vectors · doi:10.1186/s13071-024-06505-0 · Cited by 3
“This gene serves as a key transcription factor for Th1 cells, governing their development, regulating IFN-γ production, facilitating the activation of NK cells and CD8 + T cells and inhibiting the development of Th2 and Th17 cells [36].”
In silico, in vitro, and ex vivo analysis reveals miR ‐27a‐3p and miR ‐155‐5p as key microRNAs for glioblastoma progression: Insights into Th1 differentiation and apoptosis induction
Weber, A. F., Scholl, J. N., Dias, C. K., Pierdoná, V., Assmann, T. S., Anzolin, E., Kus, W. P., Worm, P. V., Battastini, A. M. O., & Figueiró, F. (2024) · The FASEB Journal · doi:10.1096/fj.202401538r · Cited by 4
“88,91 In view of the impacts of miRNA overexpression in tumor progression, some therapeutic approaches are already in development, such as miRNA sponges, antisense oligonucleotides (an-tagomiRs and antimiRs), and gene knockouts based on CRISPR/Cas9 technology.”
Usutu virus-induced meningoencephalitis in immunocompetent mice is characterized by the recruitment of mononuclear cells and a proinflammatory T helper 1 response
Rocha, R. D. P. F., Coimbra, L. D., Fontoura, M. A., Ribeiro, G., Sotorilli, G. E., Gomes, G. F., Borin, A., Felipe, J. S., Slowikowski, E., Greison, W. S. S., et al. (2025) · Journal of Virology · doi:10.1128/jvi.01724-24 · Cited by 5
“Following intracranial injection of USUV, we noted an increased expression of T-bet, a transcription factor known for its involvement in the terminal differentiation of T CD4 + lymphocytes (51).”
Knockdown of T‐bet expression in Mart‐1 27–35 ‐specific T ‐cell‐receptor‐engineered human CD 4 + CD25 − and CD 8 + T cells attenuates effector function
Jha, S. S., Chakraborty, N. G., Singh, P., Mukherji, B., & Dorsky, D. I. (2014) · Immunology · doi:10.1111/imm.12431 · Cited by 3
An aza-anthrapyrazole negatively regulates Th1 activity and suppresses experimental autoimmune encephalomyelitis
Clark, M., Leaman, D. W., Hazelhurst, L. A., Hwang, E. S., & Quinn, A. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.12.014 · Cited by 3
“To investigate whether BBR3378 altered the expression of other T-bet regulated factors we examine IL-2rβ and CXCR3 expression on T cells [26,32,33].”
Background
Function and Regulation of Age‐Associated B Cells in Diseases
Geng, Z., Cao, Y., Zhao, L., Wang, L., Dong, Y., Bi, Y., & Liu, G. (2025) · Journal of Cellular Physiology · doi:10.1002/jcp.31522 · Cited by 4
“T ‐ bet is an important transcription factor known as the T ‐ box transcription factor, which plays a key role in regulating the activation, proliferation, differentiation, life-span and effector function of T cells (Lazarevic, Glimcher, and Lord 2013).”
A peptide mimic of SOCS1 modulates equine peripheral immune cells in vitro and ocular effector functions in vivo: implications for recurrent uveitis
Stafford, L. S., Plummer, C. E., Smith, W. C., Gibson, D. J., Sharma, J., Vicuna, V., Diakite, S., & Larkin, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1513157 · Cited by 2
“While Th1 cells drive in ﬂ ammatory processes in macrophages, through the secretion of TNF a and IFN g (12, 13), the production of IL-6 and IL-17 by Th17 cells can enhance in ﬂ ammation through chemokine secretion (29, 30).”
Modulation of γδ T cells by USF3: Implications for liver fibrosis and immune regulation
Wang, X., Lin, R., Li, D., Ye, W., Yang, Z., Wu, N., Wen, Q., Tan, J., Sun, C., Yin, Z., et al. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114100 · Cited by 3
Multi-omic analysis of PBMCs in sepsis reveals widespread cytotoxic dysfunction and an increased population of CD69 expressing naïve CD4+ T cells
Flynn, J., Baird, A., Breen, E. P., Carty, M., McNevin, C. S., McDermott, L., Kenny, E. M., Coakley, J. D., Ryan, T., Doherty, D. G., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1667186 · Cited by 2
“This holds true for the sepsis population of TD CD8+ T cells 2 which display a decrease in all four TFs compared to bacteraemia cells (80), likely compounding this impairment.”
T-bet: biological functions, molecular mechanisms, and therapeutic applications: a systematic review
Yang, X., Sun, M., Tang, X., Zhang, X., & Shen, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1671806 · Cited by 2
“…demonstrates a U-shaped association with intestinal in ﬂ ammation: overexpression compromises epithelial barrier integrity and disrupts ion channel function, whereas insuf ﬁ cient expression results in dysregulated Th1/Th17 immune responses and heightened susceptibility to infections (132).”
MultiCausGRN: directed prior-guided graph attention model for multi-omics gene regulatory network inference
Alkhateeb, N. J., & Awad, M. (2026) · Frontiers in Bioinformatics · doi:10.3389/fbinf.2026.1883130 · Cited by 2
“(Lazarevic et al., 2013; Zhu, 2010).”
Th cell transcription factors: Sequence characteristics and expression profiles in Epinephelus coioides after Cryptocaryon irritans infection
Han, Q., Chen, H., Hu, Y., Han, R., Mo, Z., Luo, X., Dan, X., & Li, Y. (2021) · Aquaculture · doi:10.1016/j.aquaculture.2021.737349 · Cited by 2
Small Molecule Inhibitors Targeting Nuclear Factor κB Activation Markedly Reduce Expression of Interleukin-2, but Not Interferon-γ, Induced by Phorbol Esters and Calcium Ionophores
Tanaka, Y., Nakao, A., Miyake, Y., Higashi, Y., Tanigaki, R., & Kataoka, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313098 · Cited by 2
“Eomes is a transcription factor that specifies the lineage of T cells and NK cells [11,14,41].”
Background
Mixed T Helper1/T Helper2/T Cytotoxic Profile in Subjects with Chronic Chagas Disease with Hypersensitivity Reactions to Benznidazole
Eiro, M. D. C., Natale, M. A., Alvarez, M., Castro, A., Seigelshifer, D. J., Viotti, R. J., Fernandez, M. L., Mazzuoccolo, L. D., Lococo, B., Bertocchi, G. L., et al. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.01357-22 · Cited by 2
“T-bet (24, 25) is also involved in the differentiation of cytotoxic lymphocytes is supported”
Background
Longitudinal analysis of the impact of rituximab on circulating EBV miRNAs in three paediatric kidney transplant recipients
Hassan, J., Gonzalez, G., Stack, M., Dolan, N. M., Sweeney, C., Gascun, C. F. D., Connell, J., Awan, A., & Riordan, M. (2023) · Journal of Clinical Virology Plus · doi:10.1016/j.jcvp.2023.100171 · Cited by 2
Mucosal Immunity Related to CD8+ T Lymphocytes in Children with Helicobacter pylori Gastritis
Yang, D. H., Lee, H. Y., Choi, W., Hyun, C. L., & Kang, K. S. (2024) · Pediatric Gastroenterology Hepatology & Nutrition · doi:10.5223/pghn.2024.27.1.26 · Cited by 2
Intradermal lymphocyte therapy: A promising treatment for recurrent pregnancy loss in patients without anti-TPO antibodies
Ebrahimi, R., Asghari, K. M., Alamdary, S. J., Kamrani, A., Soltani‐Zangbar, M. S., Danaii, S., Aliasgharzadeh, A., Heris, J. A., Maleki, L. A., Hojjat‐Farsangi, M., et al. (2025) · Human Immunology · doi:10.1016/j.humimm.2024.111229 · Cited by 5
T-bet in Tfh cells: Now you see me, now you don’t
Kaech, S. M. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20181878 · Cited by 2
“It is now known that, in addition to Th1 cells, T-bet is also expressed in a plethora of other immune cells to help orchestrate type 1 immune responses to viruses and intracellular bacteria, including dendritic cells, CD8+ T cells, natural killer cells, and B cells (Lazarevic et al., 2013).”
Background
Impact de l’utilisation de la corticothérapie systémique sur l’efficacité des inhibiteurs de points de contrôle immunitaire
Hazzaz, R. E., Kfoury, M., Lavaud, P., Marabelle, A., Champiat, S., Mellas, N., Besse, B., Massard, C., & Géraud, A. (2021) · Bulletin du Cancer · doi:10.1016/j.bulcan.2021.01.015 · Cited by 2
Cell-Mediated Immunity
Rajaei, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818731-9.00038-0 · Cited by 2
Transcriptional network analysis of peripheral blood leukocyte subsets in multiple sclerosis identifies a pathogenic role for a cytotoxicity‐associated gene network in myeloid cells
Jordan, M. A., Gresle, M. M., Gemiarto, A. T., Stanley, D., Smith, L. D., Laverick, L., Spelman, T. D., Stankovich, J. M., Willson, A. M. L., Dinh, X. T., et al. (2024) · Immunology and Cell Biology · doi:10.1111/imcb.12793 · Cited by 1
“…targeted knockout mice EOMES and Tbx21 / Tbet gene (together referred to as ET ) are transcription factors controlling T-and NK-cell differentiation 20,21 and have previously been reported to bridge innate and adaptive immunity, as they are expressed in DCs, NK cells, NKT cells and innate lymphoid…”
Profile of Cytokines and T Cell Subsets Transcription Factors in Cerebrospinal Fluid of Patients with Viral Encephalitis
Tebibi, K., Laamari, R. B., Saied, Z., Maghrebi, O., Touzi, H., Meddeb, Z., Sassi, S. B., Triki, H., Belghith, M., & Rezig, D. (2024) · Viral Immunology · doi:10.1089/vim.2024.0058 · Cited by 1
“…most research has concentrated on the role of T-bet in Th1 differentiation, generally characterizing T-bet as a suppressor of Tfh differentiation (Lazarevic et al., 2013; Nakayamada et al., 2011; Oestreich et al., 2011), the precise contribution of T-bet to the Tfh cell response during acute…”
TBX21 knockdown attenuates neuroinflammation induced by intracerebral hemorrhage via the SIRT1-WDR5-H3K4me3 axis
Zou, Z., Liu, Z., Zhang, Z., & Li, X. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111415 · Cited by 1
Sepsis impairs immunocompetent plasmacytoid dendritic cell reconstitution from hematopoietic stem/progenitor cell through altered bone marrow environment
Lu, J., Lv, Z., Xue, M., Fan, D., Yang, H., Hong, Y., Wang, Y., Guo, Z.-Q., Ma, J., Huang, J., et al. (2025) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2025.106823 · Cited by 1
GATA3 regulates Th1/Th2 balance in allergic rhinitis by interacting with RUNX1
Li, Y., Wang, T., He, M., Wang, Y., & He, J. (2025) · Future Science OA · doi:10.1080/20565623.2025.2541503 · Cited by 1
“…by regulate the balance of th1/th2. interestingly, t-bet, a member of the t-box gene family; is selectively expressed in th1 cells and not only promotes th1 cell differentiation and iFN-γ secretion, but also inhibits Gata3 expression and affects il-4 signaling and th2 cell differentiation [38].”
Targeted deprivation of STAT6 sensitizes acute lymphoblastic leukemia cells to cytarabine in vivo and in vitro: clinical implications
Sun, S., Cheng, Y., Huang, X., Yan, Y., Hou, W., Fang, H., Chen, Y., Ma, C., Lu, Y., Zhou, Z., et al. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07981-7 · Cited by 1
Vitamin A deficiency enhances susceptibility to experimental autoimmune pancreatitis through activation of CD4+ T cells expressing CXCR3 and secreting CCL25
Kurimoto, M., Watanabe, T., Otsuka, Y., Hara, A., Omaru, N., Sekai, I., Masuta, Y., Masaki, S., Kamata, K., Minaga, K., et al. (2025) · Clinical & Experimental Immunology · doi:10.1093/cei/uxaf060 · Cited by 1
Essential roles of CTCF binding sites at TAD boundaries in modulating chromatin interactions and transcriptional regulation at the Ifng locus
Muto, K., Yoshida, D., Suzuki, T., Yamamoto, N., Inoue, N., Murakami, A., Iseki, K., & Sekimata, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1667851 · Cited by 1
FGD5-AS1 and Th1/Th2 imbalance in the progression of diabetic nephropathy: evidence from bioinformatic and experimental validation
Ajorlou, P., Hosseini, S. A., Ghanbarnejad, A., & Shekari, M. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01946-y · Cited by 1
“Its expression is regulated through two independent signaling pathways, IFN-γ-STAT1 and IL-12-STAT4 , which play a crucial role in differentiating naïve T cells into Th1 cells [31].”
Transforming growth factor β induced as a novel secreted immune checkpoint counterinhibiting human tumor-associated T cells
Rosado, M. M., Timperi, E., Melaiu, O., Vitale, S., Bachy, S., Grimaldi, A., Corrado, M., Mancini, V., Leonti, G., Conti, F., et al. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-012668 · Cited by 1
Inefficient megakaryopoiesis in mouse hematopoietic stem–progenitor cells lacking T-bet
Furusawa, A., Sadashivaiah, K., Singh, Z. N., Civin, C. I., & Banerjee, A. (2015) · Experimental Hematology · doi:10.1016/j.exphem.2015.11.003 · Cited by 1
“[12] Lazarevic V, Glimcher LH, Lord GM.”
The inhibition of CD4+ T cell proinflammatory response by lactic acid is independent of monocarboxylate transporter 1
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Characterization of the global bovine microRNAome of peripheral blood mononuclear cells isolated from Mycobacterium bovis exposed cattle
Karagianni, A. E., Benedictus, L., Steinbach, S., Broere, F., & van der Heijden, E. M. D. L. (2025) · Tuberculosis · doi:10.1016/j.tube.2025.102639 · Cited by 1
To Bet or Not to Bet on T-bet As a Therapeutic Target in Emphysema?
Wang, X., Rojas, J., & Owen, C. A. (2019) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2019-0118ed · Cited by 1

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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