Cited by 783T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisCytokine Signaling Pathways and Interactions

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T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells

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Lighvani, Andre A., Frucht, David M., Jankovic, Dragana, Yamane, Hidehiro, Aliberti, Julio, Hissong, Bruce D., Nguyen, Bai V., Gadina, Massimo, Sher, Alan, Paul, William E., O'Shea, John J.·2001·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.261570598PMC PMC64996

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Abstract

Differentiation of naive CD4 + T cells into IFN-γ-producing T helper 1 (T H 1) cells is pivotal for protective immune responses against intracellular pathogens. T-bet, a recently discovered member of the T-box transcription factor family, has been reported to play a critical role in this process, promoting IFN-γ production. Although terminal T H 1 differentiation occurs over days, we now show that challenge of mice with a prototypical T H 1-inducing stimulus, Toxoplasma gondii soluble extract, rapidly induced IFN-γ and T-bet; T-bet induction was substantially lower in IFN-γ-deficient mice. Naive T cells expressed little T-bet, but this transcription factor was induced markedly by the combination of IFN-γ and cognate antigen. Human myeloid antigen-presenting cells showed T-bet induction after IFN-γ stimulation alone, and this induction was antagonized by IL-4 and granulocyte/macrophage colony-stimulating factor. Although T-bet was induced rapidly and directly by IFN-γ, it was not induced by IFN-α, lipopolysaccharide, or IL-1, indicating that this action of IFN-γ was specific. Moreover, T-bet induction was dependent on Stat1 but not Stat4. These data argue for a model in which IFN-γ gene regulation involves an autocrine loop, whereby the cytokine regulates a transcription factor that promotes its own production. These findings substantially alter the current view of T-bet in IFN-γ regulation and promotion of cell-mediated immune responses.

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Background
Caerulomycin A Enhances Transforming Growth Factor-β (TGF-β)-Smad3 Protein Signaling by Suppressing Interferon-γ (IFN-γ)-Signal Transducer and Activator of Transcription 1 (STAT1) Protein Signaling to Expand Regulatory T Cells (Tregs)
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Background
Identification of an anergic BND cell–derived activated B cell population (BND2) in young-onset type 1 diabetes patients
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“In addition, given that B ND 2 cells express high levels of T-bet, we also included IFN-γ , which has been shown to induce upregulation of T-bet expression (Lighvani et al., 2001).”
Background
Radix Saposhnikovia extract suppresses mouse allergic contact dermatitis by regulating dendritic-cell-activated Th1 cells
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“…cells in the lymph nodes in the initial stage of ACD. ur data also demonstrated that RS extract downregulated the mRNA xpression of T-bet, a Th1-specific transcription factor that induces he synthesis of IFN-γ and negatively regulates the Th2 pathways Lighvani et al. 2001; Szabo et al. 2000, 2003).”
Background
Interleukin-18 directly activates T-bet expression and function via p38 mitogen-activated protein kinase and nuclear factor-κB in acute myeloid leukemia–derived predendritic KG-1 cells
Bachmann, M., Drăgoi, C. M., Poleganov, M. A., Pfeilschifter, J. M., & Mühl, H. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0505 · Cited by 29
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“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript effectors (Lighvani et al., 2001; Zhu, 2018).”
Background
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Background
Effects of LPS-mediated bystander activation in the innate immune system
Yadav, R., Zammit, D. J., Lefrançois, L., & Vella, A. T. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0406253 · Cited by 28
“In a time kinetic study, LPS exposure of myeloid cells revealed that IFN- production occurs prior to increase in T-bet mRNA [ 35 ].”
Background
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“In addition to its key role in activating macrophages [84], IFN-γ also plays a role in inducing further T-bet expression [85].”
Background
Cancer immunotherapy from biology to nanomedicine
Abdelbaky, S. B., Ibrahim, M. T., Samy, H., Mohamed, M., Mohamed, H., Mustafa, M., Abdelaziz, M. M., Forrest, M. L., & Khalil, I. A. H. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.06.025 · Cited by 28
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“Also, mRNA levels of T-bet and IFN- R (Fig.”
Influential
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“The degradation rate of T-bet and Gata3 is equal to 5 day−1 = 35 week−1 corresponding to a lifetime 4–5 hours (Grogan et al. 2001; Lighvani et al. 2001; Yates et al. 2004).”
BackgroundInfluential
Epigenetic Changes in Inflammatory and Autoimmune Diseases
Nielsen, H. M., & Tost, J. (2012) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-007-4525-4_20 · Cited by 28
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“In addition to its role in inducing the expression of IFN- , T-bet seems to induce the expression of IL-12R 2 subunit (34, 35) and is expressed by naive T cells after Stat-1-mediated IFN- signaling (34, 36).”
Background
Ustekinumab in the therapy of chronic plaque psoriasis
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“Expression of the β2 subunit of IL-12R on activated T cells and NK cells is maintained by IFNγ.(41,42) IL-12 receptor is also expressed on”
Background
T-bet inhibits innate lymphoid cell–mediated eosinophilic airway inflammation by suppressing IL-9 production
Matsuki, A., Takatori, H., Makita, S., Yokota, M., Tamachi, T., Suto, A., Suzuki, K., Hirose, K., & Nakajima, H. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.08.022 · Cited by 26
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“These data are consistent with previous reports that have demonstrated that IFN- is of critical importance for the early induction of T-bet expression during mouse Th1 cell differentiation (8, 9, 11, 13).”
Result
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“, a positive feedback loop) [65, 66].”
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“…be secondary to a defect of IL-12 in patients with NSCLC. Decreased IFN-g in the tumoral region of patients with NSCLC. T-bet directly promotes the transcription of IFNG in Th1 and Tc1 cells and is in turn induced by IFN-g via a positive feedback loop (Szabo et al, 2000; Lighvani et al, 2001).”
Background
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“…(such as STAT1 and STAT4) involved in the maintenance and di ﬀ erentiation of the Th1 immune response, which plays a key role in anti-tumor immunity, and the recruitment and activation of e ﬀ ector immune cells, such as M1 macrophages, dendritic cells and natural killer (NK) cells [45,46,50].”
Background
Direct AKT activation in tumor-infiltrating lymphocytes markedly increases interferon-γ (IFN-γ) for the regression of tumors resistant to PD-1 checkpoint blockade
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T-bet, pSTAT1 and pSTAT3 expression in peripheral blood mononuclear cells during pregnancy correlates with post-partum activation of multiple sclerosis
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Human Memory, but Not Naive, CD4+ T Cells Expressing Transcription Factor T-bet Might Drive Rapid Cytokine Production
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“Activation of STAT-1 by IFN- is important for the induction of T-bet during Th1 differentiation in vitro (15, 16).”
Background
IL-12–Dependent Cytomegalovirus-Specific CD4+ T Cell Proliferation, T-bet Induction, and Effector Multifunction during Primary Infection Are Key Determinants for Early Immune Control
Popescu, I., Pipeling, M. R., Mannem, H. C., Shah, P. D., Orens, J. B., Connors, M., Migueles, S. A., & McDyer, J. F. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1501589 · Cited by 24
“Although earlier work in the human demonstrated a role for IFNg/STAT1 signaling for T-bet induction in the human (28), the regulation of T-bet by IL-12 in human Ag-specific CD4 T cells, particularly during an acute infection, has not been previously reported to our knowledge.”
Background
WSX-1 over-expression in CD4+ T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation
Takeda, A., Hamano, S., Shiraishi, H., Yoshimura, T., Ogata, H., Ishii, K., Ishibashi, T., Yoshimura, A., & Yoshida, H. (2005) · International Immunology · doi:10.1093/intimm/dxh268 · Cited by 23
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“The transcription factor Eomesodermin (Eomes) is associated with cytolytic T cell differentiation (46), T-bet is associated with IFN-γ from T cells (47), and ROR-γT with IL17 from T cells (48).”
STAT6 activation by Toxoplasma gondii infection induces the expression of Th2 C-C chemokine ligands and B clade serine protease inhibitors in macrophage
Ahn, H., Kim, J. Y., Ryu, K.-J., & Nam, H. (2009) · Parasitology Research · doi:10.1007/s00436-009-1577-8 · Cited by 23
“Inhibition of JAK3 blocks STAT6 phosphorylation during the entry and growth of T. gondii in host cells, which suggests the mediation of STAT6 phosphorylation via JAK3 against the direct phosphorylation of STAT6 by a secreted kinase homologue from T. gondii, ROP16 (Saeij et al. 2007; Laliberte and Carruthers 2008; Buzo…”
Background
The persistency of high levels of pSTAT3 expression in circulating CD4+ T cells from CIS patients favors the early conversion to clinically defined multiple sclerosis
Frisullo, G., Nociti, V., Iorio, R., Patanella, A. K., Marti, A., Massimiliano Mirabella, A., Tonali, P. A., & Batocchi, A. P. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.09.003 · Cited by 22
“signaling pathway and once expressed, amplifies the production of IFNγ (Lighvani et al., 2001).”
Background
Decreased T-bet expression and changes in chemokine levels in adults with asthma
Ko, F. W. S., Lun, S. W., Wong, C. K., Szeto, C., Lam, C. W. K., Leung, T. F., & Hui, D. S. C. (2007) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2006.03315.x · Cited by 22
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“Its expression in macrophages (Lighvani et al, 2001), is thought to participate in regulating IL-6 expression in bone marrow-derived macrophages (Hayashi et al, 2019).”
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
“CXCR3 interaction with its ligand (CXCL10) causes chemotaxis property and recruits EPCs from BM, leading to EPCs differentiation (Ling et al., 2014).”
Background
Ruxolitinib Ameliorates Airway Hyperresponsiveness and Lung Inflammation in a Corticosteroid-Resistant Murine Model of Severe Asthma
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“It is also expressed by antigen-presenting cells (APCs), including DCs for optimal production of IFN-g and subsequent antigen-specific Th1 cell activation (45, 46).”
Background
O-GlcNAcylation and immune cell signaling: A review of known and a preview of unknown
Ramakrishnan, P. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107349 · Cited by 23
“STAT1 activation in T cells is required for T-bet expression induced by IFN g (76).”
Background
T‐bet‐dependent regulation of CD8+ T‐cell expansion during experimental Trypanosoma cruzi infection
Cobb, D. A., Guo, S., Lara, A. M., Manque, P., Buck, G. A., & Smeltz, R. B. (2009) · Immunology · doi:10.1111/j.1365-2567.2009.03169.x · Cited by 22
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
Cytokine signaling/transcription factor cross-talk in T cell activation and Th1-Th2 differentiation.
Liberman, A. C., Refojo, D., & ARZT, E. S. (2003) · PubMed · Cited by 22
High levels of eukaryotic Initiation Factor 6 (eIF6) are required for immune system homeostasis and for steering the glycolytic flux of TCR-stimulated CD4+ T cells in both mice and humans
Manfrini, N., Ricciardi, S., Miluzio, A., Fedeli, M., Scagliola, A., Gallo, S., Brina, D., Adler, T., Busch, D. H., Gailus‐Durner, V., et al. (2017) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2017.07.022 · Cited by 22
“IFN-γ levels for each sample were 212 normalized to total protein content.”
BackgroundInfluential
Dihydrotanshinone I Alleviates Crystalline Silica-Induced Pulmonary Inflammation by Regulation of the Th Immune Response and Inhibition of STAT1/STAT3
Zhang, Y., Li, C. R., Li, S., Lu, Y., Du, S., Zeng, X., Chen, X., & Chen, J. (2019) · Mediators of Inflammation · doi:10.1155/2019/3427053 · Cited by 22
Differential interferon‐gamma production potential among naïve CD 4+ T cells exists prior to antigen encounter
Sood, A., Lebel, M., Fournier, M., Rogers, D., Mandl, J. N., & Melichar, H. J. (2019) · Immunology and Cell Biology · doi:10.1111/imcb.12287 · Cited by 22
T-bet and pSTAT-1 expression in PBMC from coeliac disease patients: new markers of disease activity
Frisullo, G., Nociti, V., Iorio, R., Patanella, A. K., Plantone, D., Bianco, A. D., Marti, A., Cammarota, G., Tonali, P., & Batocchi, A. P. (2009) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2009.03999.x · Cited by 22
Altered TH1, TH2, TH17 balance in assisted reproductive technology conceived mice
Ahmadi, H., Fathi, F., Karimi, H., Amidi, F., Mehdinejadiani, S., Moeini, A., rezai, M. B., Hoseini, S., & Sobhani, A. (2020) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2020.103117 · Cited by 21
Interferon-γ-producing B cells induce the formation of gastric lymphoid follicles after Helicobacter suis infection
Yang, L., Yamamoto, K., Nishiumi, S., Nakamura, M., Matsui, H., Takahashi, S., Dohi, T., Okada, T., Kakimoto, K., Hoshi, N., et al. (2014) · Mucosal Immunology · doi:10.1038/mi.2014.66 · Cited by 21
Pyrin-only protein 2 limits inflammation but improves protection against bacteria
Periasamy, S., Porter, K. A., Atianand, M., Le, H. T., Earley, S., Duffy, E. B., Haller, M. C., Chin, H., & Harton, J. A. (2017) · Nature Communications · doi:10.1038/ncomms15564 · Cited by 21
The CD70–CD27 interaction during the stimulation with dendritic cells promotes naive CD4+ T cells to develop into T cells producing a broad array of immunostimulatory cytokines in humans
岡田, 睦., Kitawaki, T., Kadowaki, N., Iwata, S., Morimoto, C., Hori, T., & Uchiyama, T. (2009) · International Immunology · doi:10.1093/intimm/dxp056 · Cited by 21
NADPH Oxidase 2–Derived Reactive Oxygen Species Promote CD8+ T Cell Effector Function
Chen, J., Liu, C., Chernatynskaya, A., Newby, B. N., Brusko, T. M., Xu, Y., Barra, J. M., Morgan, N. N., Santarlas, C., Reeves, W. H., et al. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2200691 · Cited by 21
IFN-γ and T-bet Expression in Human Dendritic Cells from Normal Donors and Cancer Patients Is Controlled through Mechanisms Involving ERK-1/2-Dependent and IL-12-Independent Pathways
Li, H., Wojciechowski, W., Dell’Agnola, C., Lopez, N. E., & Espinoza‐Delgado, I. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.3554 · Cited by 20
“More recently, T-bet has been reported to be expressed in myeloid cells where it is required for optimal production of IFN- (26, 28).”
Background
Different T‐bet expression patterns characterize particular reactive lymphoid tissue lesions
Jöhrens, K., Anagnostopoulos, I., Dürkop, H., & Stein, H. (2005) · Histopathology · doi:10.1111/j.1365-2559.2005.02305.x · Cited by 20
Virus-specific CD4 and CD8 T cell responses in the absence of Th1-associated transcription factors
Mollo, S. B., Ingram, J. T., Kress, R. L., Zajac, A. J., & Harrington, L. E. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.0813429 · Cited by 19
“In differentiating CD4 Th1 cells, Tbet is induced via TCR and IFN- signaling [2, 8, 9] and is integral for the generation of effector CD4 T cell responses to intracellular pathogens [10].”
Background
mTOR sustains inflammatory response in celiac disease
Sedda, S., Dinallo, V., Marafini, I., Franzè, E., Paoluzi, O. A., Izzo, R., Giuffrida, P., Sabatino, A. D., Corazza, G. R., & Monteleone, G. (2020) · Scientific Reports · doi:10.1038/s41598-020-67889-4 · Cited by 20
Leuconostoc citreum HJ‐P4 (KACC 91035) regulates immunoglobulin E in an ovalbumin‐induced allergy model and induces interleukin‐12 through nuclear factor‐kappa B and p38/c‐Jun N‐terminal kinases signaling in macrophages
Kang, H. G., Oh, Y., Ahn, K.-S., Eom, H., Han, N., Kim, Y., & Sohn, N. (2009) · Microbiology and Immunology · doi:10.1111/j.1348-0421.2009.00131.x · Cited by 20
Induction of IL-12 Production in Human Peripheral Monocytes byTrypanosoma cruziIs Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γand CD40-CD40L Interactions
Abel, L. C. J., Ferreira, L. R. P., Navarro, I. C., Baron, M., Kalil, J. E., Gazzinelli, R. T., Rizzo, L. V., & Cunha‐Neto, E. (2014) · Mediators of Inflammation · doi:10.1155/2014/345659 · Cited by 20
“It was shown that IFNγ stimulus also upregulates the transcription factor T-bet [42], which in turn maintains IL-12Rβ chain expression [43], possibly resulting in a positive feedback loop that, consequently, keeps the shift towards a Th1 response in Chagas”
Background
A Virtual Culture of CD4+ T Lymphocytes
Mendoza, L. (2013) · Bulletin of Mathematical Biology · doi:10.1007/s11538-013-9814-9 · Cited by 19
ID2 and ID3 are indispensable for Th1 cell differentiation during influenza virus infection in mice
Han, X., Liu, H., Huang, H., Liu, X., Jia, B., Gao, G. F., & Zhang, F. (2018) · European Journal of Immunology · doi:10.1002/eji.201847822 · Cited by 19
Modelling of Immune Checkpoint Network Explains Synergistic Effects of Combined Immune Checkpoint Inhibitor Therapy and the Impact of Cytokines in Patient Response
Kondratova, M., Barillot, E., Zinovyev, A. Y., & Calzone, L. (2020) · Cancers · doi:10.3390/cancers12123600 · Cited by 19
“The activation of cytokines, such as IFNG and IL12, upregulates the expression of Tbet via STAT1 and STAT4 pathways, respectively [61,62].”
Background
Sustained Post-Developmental T-Bet Expression Is Critical for the Maintenance of Type One Innate Lymphoid Cells In Vivo
Schroeder, J.-H., Roberts, L. B., Meissl, K., Lo, J. W., Hromadová, D., Hayes, K. S., Zabinski, T., Read, E., Heliodoro, C. M., Reis, R. A. D., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.760198 · Cited by 19
Modulation of Th1 and Th2 responses for immunotherapy
Dumont, F. J. (2002) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.12.3.341 · Cited by 19
“Tbet appears to act upstream of the Stat4 pathway, to initiate chromatin remodelling of IFN-γ alleles and IL-12Rβ2 expression, thereby rendering T-cells competent to Stat4 activation [58], and its expression is upregulated by IFN-γ [59].”
Background
Association study of 15 novel single‐nucleotide polymorphisms of the T‐bet locus among Finnish asthma families
Ylikoski, E. K., Kinos, R., Sirkkanen, N., Pykäläinen, M., Savolainen, J., Laitinen, L. A., Kere, J., Laitinen, T., & Lahesmaa, R. (2004) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2004.01995.x · Cited by 19
Allies or enemies? The effect of regulatory T cells and related T lymphocytes on the profibrotic environment in bleomycin-injured lung mouse models
Mutlu, S. M., Scalise, M. C., Philip, S., Gazdhar, A., & Fabian, B. (2022) · Clinical and Experimental Medicine · doi:10.1007/s10238-022-00945-7 · Cited by 18
“The T box transcription factor TBX21 (Tbet) is known to be an important transcription factor leading to Th1 immune response and IFNγ production [80, 81].”
Background
Interferon-γ
Schreiber, G., & Schreiber, R. D. (2003) · Elsevier eBooks · doi:10.1016/b978-012689663-3/50028-4 · Cited by 19
An Eimeria maxima Antigen: Its Functions on Stimulating Th1 Cytokines and Protective Efficacy Against Coccidiosis
Chen, C., Zhang, Y., Liu, J., Wang, M., Lu, M., Xu, L., Yan, R., Li, X., & Song, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.872015 · Cited by 17
The FoxO4/DKK3 axis represses IFN-γ expression by Th1 cells and limits antimicrobial immunity
Chen, X. '., Hu, J., Wang, Y., Lee, Y., Zhao, X., Li, J., Zhu, G., Wang, H., Jiang, Y., Liu, F., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci147566 · Cited by 22
ProtectiveToxoplasma gondii-Specific T-Cell Responses Require T-Cell-Specific Expression of Protein Kinase C-Theta
Nishanth, G., Sakowicz‐Burkiewicz, M., Händel, U., Kliche, S., Wang, X., Naumann, M., Deckert, M., & Schlüter, D. (2010) · Infection and Immunity · doi:10.1128/iai.01407-09 · Cited by 17
STAT4 Regulates Antiviral Gamma Interferon Responses and Recurrent Disease during Herpes Simplex Virus 2 Infection
Svensson, A., Tunbäck, P., Nordström, I., Shestakov, A., Padyukov, L., & Eriksson, K. (2012) · Journal of Virology · doi:10.1128/jvi.00947-12 · Cited by 18
Topical Application of Interleukin-28A Attenuates Allergic Conjunctivitis in an Ovalbumin-Induced Mouse Model
Chen, J., Zhang, J., Zhao, R., Jin, J., Yu, Y., Li, W., Wang, W., Zhou, H., & Su, S. B. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18457 · Cited by 17
STAT1 signaling is required for optimal Th1 cell differentiation in mice
Ma, D., Huang, H., & Huang, Z. (2010) · Chinese Science Bulletin · doi:10.1007/s11434-010-0030-9 · Cited by 19
The effect of centaurein on interferon-γ expression and Listeria infection in mice
Chang, S.-L., Yeh, H.-H., Lin, Y.-S., Chiang, Y., Wu, T., & Yang, W. (2006) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2006.11.026 · Cited by 17
“IFN-γ was reported to induce T-bet expression (Lighvani et al., 2001), raising the possibility that the up-regulation of T-bet is an indirect consequence of centaurein inducing IFN-γ.”
Background
Function of CD27 in helper T cell differentiation
Libregts, S. F. W. M., van Olffen, R. W., van der Sluijs, K. F., van Lier, R. A. W., & Nolte, M. A. (2011) · Immunology Letters · doi:10.1016/j.imlet.2011.01.008 · Cited by 17
Stimulation of an anti-tumor immune response with “chromatin-damaging” therapy
Chen, M., Brackett, C. M., Burdelya, L. G., Punnanitinont, A., Patnaik, S. K., Matsuzaki, J., Odunsi, A., Gudkov, A. V., Singh, A. K., Repasky, E. A., et al. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02846-8 · Cited by 16
STAT1 is Involved in the Pathogenesis of Murine Allergic Rhinitis
Hattori, H., Rosas, L. E., Okano, M., Durbin, J. E., Nishizaki, K., & Satoskar, A. R. (2007) · American Journal of Rhinology · doi:10.2500/ajr.2007.21.2970 · Cited by 18
New interleukins: are there any more?
Gadina, M., Ferguson, P., & Johnston, J. A. (2003) · Current Opinion in Infectious Diseases · doi:10.1097/00001432-200306000-00005 · Cited by 18
Self-citation
THEMIS enhances the magnitude of normal and neuroinflammatory type 1 immune responses by promoting TCR-independent signals
Yang, C., Blaize, G., Marrocco, R., Rouquié, N., Bories, C., Gador, M., Mélique, S., Joulia, E., Benamar, M., Dejean, A. S., et al. (2022) · Science Signaling · doi:10.1126/scisignal.abl5343 · Cited by 18
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
T‐bet‐mediated Tim‐3 expression dampens monocyte function during chronic hepatitis C virus infection
Yi, W., Zhang, P., Liang, Y., Zhou, Y., Shen, H., Fan, C., Moorman, J. P., Yao, Z. Q., Zhansheng, J., & Zhang, Y. (2016) · Immunology · doi:10.1111/imm.12686 · Cited by 16
Immunological Impact of Intestinal T Cells on Metabolic Diseases
Zhou, H., Wang, L., & Liu, F. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.639902 · Cited by 19
Onecut transcription factor OC2 is a direct target of T-bet in type-1 T-helper cells
Furuno, K., Ikeda, K., Hamano, S., Fukuyama, K., Sonoda, M., Hara, T., Sasazuki, T., & Yamamoto, K. (2008) · Genes and Immunity · doi:10.1038/gene.2008.18 · Cited by 16
HLA-DR4–Associated T and B Cell Responses to Specific Determinants on the IA-2 Autoantigen in Type 1 Diabetes
McLaughlin, K. A., Gulati, K., Richardson, C. C., Morgan, D., Bodansky, H. J., Feltbower, R. G., & Christie, M. R. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301902 · Cited by 16
Enfermedad inflamatoria intestinal: Una mirada inmunológica
Sepúlveda, S. E., Beltrán, C. J., Peralta, A. B., Rivas, P., Rojas, N., Figueroa, C., Quera, R., & Hermoso, M. A. (2008) · Revista médica de Chile · doi:10.4067/s0034-98872008000300014 · Cited by 16

Authors: Lighvani, A. A., Frucht, D. M., Jankovic, D., Yamane, H., Aliberti, J., Hissong, B. D., Nguyen, B. V., Gadina, M., Sher, A., Paul, W. E., & O'Shea, J. J.
Affiliations: National Institutes of Health (US)
Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Immunobiology Section, Laboratory of Parasitic Diseases, and Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Cell Biology Laboratory, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
Corresponding author: Frucht, David M.
ORCID: Frucht, David M.
Jankovic, Dragana
Yamane, Hidehiro
Gadina, Massimo
Sher, Alan
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2001-12-18
Volume: 98
Issue: 26
Pages: 15137-15142
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.261570598
PMC: PMC64996
OpenAlex: W2011754426
Cited by: 783
References: 23
Citations by year: 2026: 14 · 2025: 20 · 2024: 17 · 2023: 30 · 2022: 25 · 2021: 25 · 2020: 23 · 2019: 18 · 2018: 26 · 2017: 20 · 2016: 23 · 2015: 24 · 2014: 43 · 2013: 34 · 2012: 40
FWCI: 13.58
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
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 › Cytokine Signaling Pathways and Interactions
Keywords: T-bet, interferon-gamma, Toxoplasma gondii, STAT1, autocrine loop, IL-4, GM-CSF, myeloid antigen-presenting cells, naive CD4+ T cells, T-box transcription factor, cell-mediated immunity
MeSH terms: T-bet Transcription Factor, Animals, Antibodies, Monoclonal, Base Sequence, Cell Differentiation, Cells, Cultured, Dendritic Cells, Female, Humans, Interferon-gamma, Macrophages, Mice, Inbred C57BL, Transcription Factors, CD4-Positive T-Lymphocytes, Up-Regulation, DNA Primers, T-Box Domain Proteins, Mice

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T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells

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