Expression of IFN regulatory factor family proteins in lymphocytes. Induction of Stat-1 and IFN consensus sequence binding protein expression by T cell activation
Abstract
Interferon consensus sequence binding protein (ICSBP) is a transcription factor of the IFN regulatory factor (IRF) family. Evidence indicates that this family has a function in the immune system. Unlike other members of the family, ICSBP is expressed exclusively in the immune system. In this work, immunoblot analysis was performed to study expression of ICSBP and other members of the family in various murine lymphocytes. The results show that all IRF family members are expressed constitutively in B cells throughout development, and in resting and activated cells. In contrast, ICSBP expression was undetectable in thymocytes and resting T cells, while all other IRF proteins tested (IRF-1, IRF-2, and ISGF3-γ) were detected in these cells. Induction of ICSBP (and weakly IRF-1, but not other members) was observed upon activation of T cells following anti-CD3 Ab binding or Con A stimulation. Once T cells were activated, ICSBP was expressed stably in both Th1 and Th2 cells. We show that Stat-1, which binds to the IFN-γ-responsive element of the ICSBP promoter, was induced following anti-CD3 Ab and Con A stimulation. Stat-1 induction was found in T cells of IFN-γ+/+, but not of IFN-γ-/- mice, indicating that T cell activation stimulates the Stat pathway of transcription that is mediated through IFN-γ. IFN-γ-activated Stat-1 partly accounted for ICSBP induction in activated T cells, as levels of induction were lower in IFN-γ-/- than in IFN+/+ T cells. Taken together, these results show that activation of ICSBP is coupled with T cell activation that is partly due to IFN-γ-induced Stat-1.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ICSBP/IRF-8 is an IFN-γ-inducible transcription factor of the IRF family that regulates transcription through multiple target DNA elements, including ISRE, EICE, and GAS.
“Interferon (IFN) consensus sequence binding protein (ICSBP)/IFN regulatory factor (IRF)-8 is an IFN g -inducible transcription factor of the IRF family and regulates transcription through multiple target DNA elements, such as IFN-stimulated response element (ISRE), Ets/IRF composite element, and IFNg activation site (GAS).”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [12]
ICSBP is expressed in hematopoietic cells, including monocyte/macrophage lineage, B lymphocytes, and activated T lymphocytes, and is inducible by IFN-γ in these cells.
“ICSBP is expressed in the hematopoietic cells, including cells of the monocyte/macrophage lineage, B lymphocytes, and activated T lymphocytes, and is inducible by IFNg in these cells, suggesting its role in immune cells. (6,9-13)”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [12]
Cited by
Sorted by citations
CELLULAR RESPONSES TO INTERFERON-γ
Boehm, U., Klamp, T., Groot, M., & Howard, J. C. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.749 · Cited by 2,890 · see citing works
Interleukin-18 Regulates Both Th1 and Th2 Responses
Nakanishi, K., Yoshimoto, T., Tsutsui, H., & Okamura, H. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.423 · Cited by 1,310 · see citing works
The IRF Family Transcription Factors in Immunity and Oncogenesis
Tamura, T., Yanai, H., Savitsky, D., & Taniguchi, T. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090400 · Cited by 1,259 · see citing works
NAKANISHI, K., YOSHIMOTO, T., Tsutsui, H., & Okamura, H. (2001) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(00)00015-0 · Cited by 658 · see citing works
Holtschke, T., Löhler, J., Kanno, Y., Fehr, T., Giese, N., Rosenbauer, F., Lou, J., Knobeloch, K.-P., Gabriele, L., Waring, J. F., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81348-3 · Cited by 644 · see citing works
Self-citationInterferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis
Zhao, B., Takami, M., Yamada, A., Wang, X., Koga, T., Hu, X., Tamura, T., Ozato, K., Choi, Y., Ivashkiv, L. B., et al. (2009) · Nature Medicine · doi:10.1038/nm.2007 · Cited by 313 · see citing works
Self-citationICSBP Directs Bipotential Myeloid Progenitor Cells to Differentiate into Mature Macrophages
Tamura, T., Nagamura-Inoue, T., Shmeltzer, Z., Kuwata, T., & Ozato, K. (2000) · Immunity · doi:10.1016/s1074-7613(00)00016-9 · Cited by 305 · see citing works
Self-citationIFNγ signaling—Does it mean JAK–STAT?
Gough, D. J., Levy, D. E., Johnstone, R. W., & Clarke, C. J. (2008) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2008.08.004 · Cited by 290 · see citing works
“IRF-8 is specifically activated by IFNg, not IFNa/b [63,64]; however its expression is restricted to macrophage and lymphoid lineages, where it can co-operate with other transcription factors including PU.”
BackgroundTWEAK Attenuates the Transition from Innate to Adaptive Immunity
Maecker, H. L., Varfolomeev, E. E., Kischkel, F. C., Lawrence, D. A., LeBlanc, H. N., Lee, W. P., Hurst, S. D., Danilenko, D. M., Li, J., Filvaroff, E. H., et al. (2005) · Cell · doi:10.1016/j.cell.2005.09.022 · Cited by 240 · see citing works
“TWEAK Inhibits STAT-1 Activation and Promotes p65 NF-kB Association with HDAC-1 To investigate how TWEAK deletion might promote the production of IFN-g and IL-12, we examined the activity of the signal transducer and activator of transcription (STAT)-1, which is key to pathogen-induced expression of IFN-g in NK cells…”
Scharton-Kersten, T., Contursi, C., Masumi, A., Sher, A., & Ozato, K. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.9.1523 · Cited by 217 · see citing works
Self-citationRoles of interferon-regulatory factors in T-helper-cell differentiation
Lohoff, M. D., & Mak, T. W. (2005) · Nature reviews. Immunology · doi:10.1038/nri1552 · Cited by 214 · see citing works
Cassatella, M. A., Gasperini, S., Bovolenta, C., Calzetti, F., Vollebregt, M., Scapini, P., Marchi, M., Suzuki, R., Suzuki, A., & Yoshimura, A. (1999) · Blood · doi:10.1182/blood.v94.8.2880.420k31_2880_2889 · Cited by 209 · see citing works
Lack of Interferon Consensus Sequence Binding Protein (ICSBP) Transcripts in Human Myeloid Leukemias
Schmidt, M., Nagel, S., Proba, J., Thiede, C., Ritter, M., Waring, J. F., Rosenbauer, F., Huhn, D., Wittig, B., Horak, I., et al. (1998) · Blood · doi:10.1182/blood.v91.1.22 · Cited by 199 · see citing works
Wang, I.-M., Contursi, C., Masumi, A., Ma, X., Trinchieri, G., & Ozato, K. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.1.271 · Cited by 187 · see citing works
“ment strongly induced the expression, as expected (19, 20).”
BackgroundMethodSelf-citationReview: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells
Tamura, T., & Ozato, K. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452755 · Cited by 183 · see citing works
Self-citationMUM1/IRF4 expression as a frequent event in mature lymphoid malignancies
Tsuboi, K., Iida, S., Inagaki, H., Kato, M., Hayami, Y., Hanamura, I., Miura, K., Harada, S., Kikuchi, M., Komatsu, H., et al. (2000) · Leukemia · doi:10.1038/sj.leu.2401696 · Cited by 177 · see citing works
IFN-γ Represses IL-4 Expression via IRF-1 and IRF-2
Elser, B., Lohoff, M. D., Kock, S., Giaisi, M., Kirchhoff, S., Krammer, P. H., & Li‐Weber, M. (2002) · Immunity · doi:10.1016/s1074-7613(02)00471-5 · Cited by 172 · see citing works
Regulation of IL4 gene expression by T cells and therapeutic perspectives
Li‐Weber, M., & Krammer, P. H. (2003) · Nature reviews. Immunology · doi:10.1038/nri1128 · Cited by 171 · see citing works
Cyclosporin A-Sensitive Transcription Factor Egr-3 Regulates Fas Ligand Expression
Mittelstadt, P. R., & Ashwell, J. D. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.3744 · Cited by 163 · see citing works
“In T cells, gamma interferon-regulated protein family members IRF-1, IRF-2, and ISGF3g are expressed constitutively, whereas ICSBP is induced upon activation (47).”
BackgroundSharf, R., Meraro, D., Azriel, A., Thornton, A. M., Ozato, K., Petricoin, E. F., Larner, A. C., Schaper, F., Hauser, H., & Levi, B.-Z. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.15.9785 · Cited by 162 · see citing works
Self-citationGiese, N. A., Gabriele, L., Doherty, T. M., Klinman, D. M., Tadesse-Heath, L., Contursi, C., Epstein, S. L., & Morse, H. C. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.9.1535 · Cited by 160 · see citing works
“Since ICSBP is expressed in activated but not resting T cells (6), some of the abnormalities exhibited by T cells of infected ICSBP2/2 mice may be attributable to altered expression of genes containing ISREs.”
Self-citationIRF8 regulates B-cell lineage specification, commitment, and differentiation
Wang, H., Lee, C. H., Qi, C., Tailor, P. B., Feng, J., Abbasi, S., Atsumi, T., & Morse, H. C. (2008) · Blood · doi:10.1182/blood-2008-01-129049 · Cited by 140 · see citing works
Hao, S. X., & Ren, R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.4.1149-1161.2000 · Cited by 143 · see citing works
“Consistent with this idea, ICSBP is expressed constitutively throughout B-cell development and in both resting and activated cells under physiological conditions (25), suggesting that ICSBP at least does not inhibit the proliferation of Blymphoid cells.”
Blanco, J. C. G., Contursi, C., Salkowski, C. A., DeWitt, D. L., Ozato, K., & Vogel, S. N. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.12.2131 · Cited by 137 · see citing works
Self-citationKuo, T. C., & Calame, K. L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.9.5556 · Cited by 132 · see citing works
“IRF-1 and IRF-2 levels remain constant during B cell development (57), while Blimp-1 is induced during terminal differentiation to plasma cells (2, 6–8, 58).”
BackgroundThe role of interferon regulatory factors in the interferon system and cell growth control
Harada, H., Taniguchi, T., & Tanaka, N. (1998) · Biochimie · doi:10.1016/s0300-9084(99)80017-0 · Cited by 131 · see citing works
Masumi, A., Wang, I.-M., Lefebvre, B., Yang, X.-J., Nakatani, Y., & Ozato, K. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.1810 · Cited by 124 · see citing works
Self-citationSalem, S., Salem, D., & Gros, P. (2020) · Human Genetics · doi:10.1007/s00439-020-02154-2 · Cited by 124 · see citing works
Grayfer, L., García-García, E., & Belosevic, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.096925 · Cited by 125 · see citing works
IRF-1: the transcription factor linking the interferon response and oncogenesis
Taniguchi, T., Lamphier, M. S., & Tanaka, N. (1997) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(97)00014-0 · Cited by 121 · see citing works
Marecki, S., Riendeau, C. J., Liang, M. D., & Fenton, M. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.11.6829 · Cited by 111 · see citing works
“An expression plasmid encoding the full-length murine ICSBP protein was provided by Keiko Ozato (National Institutes of Health, Bethesda, MD) and was previously described (39).”
IL-12 Induces IFN Regulating Factor-1 (IRF-1) Gene Expression in Human NK and T Cells
Galon, J., Sudarshan, C., Ito, S., Finbloom, D. S., & O’Shea, J. J. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.12.7256 · Cited by 101 · see citing works
Modulation of Human Immunodeficiency Virus 1 Replication by Interferon Regulatory Factors
Sgarbanti, M., Borsetti, A., Moscufo, N., Bellocchi, M. C., Ridolfi, B., Nappi, F., Marsili, G., Marziali, G., Coccia, E. M., Ensoli, B., et al. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20010753 · Cited by 91 · see citing works
“IRF-1 that is present at discrete levels in activated but not in resting T cells (51) can thus contribute to viral reactivation even in the absence of Tat.”
BackgroundResultThe IFN Regulatory Factor Family Participates in Regulation of Fas Ligand Gene Expression in T Cells
Chow, W. A., Fang, J., & Yee, J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.7.3512 · Cited by 90 · see citing works
“This result is consistent with a previous report that neither IRF-1 nor IRF-2 protein levels are induced by TCR stimulation (35).”
BackgroundMethodResultInfluentialMiyagawa, F., Zhang, H., Terunuma, A., Ozato, K., Tagaya, Y., & Katz, S. I. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201453109 · Cited by 91 · see citing works
Self-citationThe interferon regulatory factors and oncogenesis
Tanaka, N., & Taniguchi, T. (2000) · Seminars in Cancer Biology · doi:10.1006/scbi.2000.0310 · Cited by 85 · see citing works
Interferon Regulatory Factors in Hematopoietic Cell Differentiation and Immune Regulation
Battistini, A. (2009) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2009.0030 · Cited by 84 · see citing works
Tsujimura, H., Nagamura‐Inoue, T., Tamura, T., & Ozato, K. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.3.1261 · Cited by 82 · see citing works
“Unlike many other IRF members, ICSBP is expressed only in hemopoietic cells and is induced by IFN- (10, 11).”
BackgroundSelf-citationSharma, M., Sharma, S., Roy, S., et al. (2007) · Immunology and Cell Biology · doi:10.1038/sj.icb.7100037 · Cited by 79 · see citing works
Schmidt, M., Hochhaus, A., Nitsche, A., Hehlmann, R., & Neubauer, A. (2001) · Blood · doi:10.1182/blood.v97.11.3648 · Cited by 77 · see citing works
Gualco, G., Weiss, L. M., & Bacchi, C. E. (2010) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0b013e3181cf1126 · Cited by 78 · see citing works
Sol, V. V., & Fresno, M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.5.2825 · Cited by 77 · see citing works
Horiuchi, M., Wakayama, K., Itoh, A., Kawai, K., Pleasure, D., Ozato, K., & Itoh, T. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-227 · Cited by 76 · see citing works
“Rabbit anti-IRF8 antibody was reported previously [18].”
Self-citationSchaefer, B. C., Paulson, E. J., Strominger, J., & Speck, S. H. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.2.873 · Cited by 82 · see citing works
Contursi, C., Wang, I.-M., Gabriele, L., Gadina, M., O'Shea, J., Morse, H. C., & Ozato, K. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.1.91 · Cited by 72 · see citing works
Self-citationWang, H., Yan, M., Sun, J., Jain, S., Yoshimi, R., Abolfath, S. M., Ozato, K., Coleman, W. G., Ng, A. P., Metcalf, D., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301939 · Cited by 71 · see citing works
“We therefore conclude that expression of IRF8-EGFP, similar to IRF8 native proteins in stimulated B and T cells (40), is markedly upregulated in activated B and T cells.”
ResultSelf-citationReview: ICSBP/IRF-8 Transactivation: A Tale of Protein-Protein Interaction
Levi, B.-Z., Hashmueli, S., Gleit-Kielmanowicz, M., Azriel, A., & Meraro, D. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452764 · Cited by 70 · see citing works
Lew, W., Lee, E.-Y., & Krueger, J. G. (2004) · British Journal of Dermatology · doi:10.1111/j.0007-0963.2004.05891.x · Cited by 70 · see citing works
Petanidis, S., Anestakis, D., Argyraki, M., Hadzopoulou‐Cladaras, M., & Salifoglou, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073616 · Cited by 67 · see citing works
“In addition, IFN-c also has important immunoregulatory functions, including activation of macrophages, induction of antiproliferative effects on transformed cells, and can potentiate antiviral and antitumor effects of the type brought about by interferons such as IFN-a and IFN-b1a [35].”
BackgroundIRF8‐dependent Molecular Complexes Control the Th9 Transcriptional Program
Humblin, E., Thibaudin, M., Chalmin, F., Derangère, V., Limagne, E., Richard, C., Flavell, R. A., Chevrier, S., Ladoire, S., Berger, H., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01070-w · Cited by 67 · see citing works
Xiong, H., Zhu, C. Y., Li, H., Chen, F., Mayer, L., Ozato, K., Unkeless, J. C., & Plevy, S. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209583200 · Cited by 64 · see citing works
Self-citationRoles of Interleukin-18 in Tissue Destruction and Compensatory Reactions
Kashiwamura, S., Ueda, H., & Okamura, H. (2002) · Journal of Immunotherapy · doi:10.1097/00002371-200203001-00002 · Cited by 63 · see citing works
“1 binding site is located in the upstream of exon 1 (5,6).”
BackgroundRegulation of IFN Consensus Sequence Binding Protein Expression in Murine Macrophages
Kantakamalakul, W., Politis, A. D., Marecki, S., Sullivan, T., Ozato, K., Fenton, M. J., & Vogel, S. N. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.12.7417 · Cited by 61 · see citing works
Self-citationIRF8: Mechanism of Action and Health Implications
Moorman, H. R., Reategui-Almonacid, Y., Poschel, D. B., & Liu, K. (2022) · Cells · doi:10.3390/cells11172630 · Cited by 63 · see citing works
Yang, T., Wang, R., Zhang, J., et al. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117456 · Cited by 60 · see citing works
McDonald, P. P., Bovolenta, C., & Cassatella, M. A. (1998) · Biochemistry · doi:10.1021/bi972539o · Cited by 59 · see citing works
Schmidt, M., Bies, J., Tamura, T., Ozato, K., & Wolff, L. (2004) · Blood · doi:10.1182/blood-2003-01-0285 · Cited by 58 · see citing works
Self-citationShin, D., Lee, C., & Morse, H. C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027384 · Cited by 55 · see citing works
“normal mouse B cells and lymphoma cell lines with features of pro-B and pre-B cells but not by plasmacytomas, tumors of mature plasma cells [13].”
BackgroundSchmidt, M., Hochhaus, A., König-Merediz, S. A., Brendel, C. A., Proba, J., Hoppe, G. J., Wittig, B., Ehninger, G., Hehlmann, R., & Neubauer, A. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.19.3331 · Cited by 51 · see citing works
Fagerlie, S. R., Diaz, J., Christianson, T. A., McCartan, K., Keeble, W. W., Faulkner, G. R., & Bagby, G. C. (2001) · Blood · doi:10.1182/blood.v97.10.3017 · Cited by 43 · see citing works
Xiong, H., Li, H., Kong, H. J., Chen, Y., Zhao, J., Xiong, S., Huang, B., Gu, H., Mayer, L., Ozato, K., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414296200 · Cited by 44 · see citing works
Self-citationBovolenta, C., Gasperini, S., McDonald, P. P., & Cassatella, M. A. (1998) · PubMed · Cited by 44 · see citing works
Bovolenta, C., Gasperini, S., McDonald, P. P., & Cassatella, M. A. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.2.911 · Cited by 43 · see citing works
Wu, C. Y., Maeda, H., Contursi, C., Ozato, K., & Seder, R. A. (1999) · PubMed · Cited by 38 · see citing works
Self-citationMyocardial Remodeling in Diabetic Cardiomyopathy Associated with Cardiac Mast Cell Activation
Huang, Z. G., Jin, Q., Fan, M., Cong, X. L., Han, S. F., Gao, H., & Shan, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060827 · Cited by 39 · see citing works
“IFN-c is a marker not only of mast cell activation, but is also used to identify T-cell activation [39].”
RetractedPARP-14 Binds Specific DNA Sequences to Promote Th2 Cell Gene Expression
Riley, J. P., Kulkarni, A., Mehrotra, P., Koh, B., Perumal, N. B., Kaplan, M. H., & Goenka, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083127 · Cited by 38 · see citing works
“We observed that Irf1, Stat1 and Stat4 involved in Th1 differentiation [33,34,35,36] were negatively regulated by PARP-14 and ART enzyme activity (Figure 2).”
BackgroundMartı́nez, A., Pittaluga, S., Rudelius, M., DAVIES-HILL, T. M., Sebasigari, D., Fountaine, T. J., Hewitt, S. M., Jaffe, E. S., & Raffeld, M. A. (2008) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e318166f46a · Cited by 38 · see citing works
“Unlike other members of the IRF family, IRF4 is not IFN responsive, but instead, seems to be modulated by stimuli known to induce lymphocyte activation and differentiation, such as conconavalin A, staphylococcal enterotoxin A, lipopolysaccharide, interleukin (IL)-4, engagement of the CD40 receptor, and engagement of t…”
BackgroundB cells from periodontal disease patients express surface Toll-like receptor 4
Shin, H., Zhang, Y., Jagannathan‐Bogdan, M., Hastürk, H., Kantarcı, A., Liu, H., Dyke, T. E. V., Ganley-Leal, L. M., & Nikolajczyk, B. S. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0708428 · Cited by 36 · see citing works
“1, IRF-4, and IRF-8 are constitutively expressed in normal B cells [34–36], and the TLR4 promoter is constitutively accessible, these transcription factors do not associate with the TLR4 promoter (Fig.”
BackgroundInterferon a and T-cell responses in chronic myeloid leukemia
Burchert, A., & Neubauer, A. (2004) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428190400012029 · Cited by 33 · see citing works
“[82] Nelson N, Kanno Y, Hong C, Contursi C, Fujita T, Fowlkes BJ, O’Connell E, Hu-Li J, Paul WE, Jankovic D, Sher AF, et al.”
BackgroundWu, C.-Y., Maeda, H., Contursi, C., Ozato, K., & Seder, R. A. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.2.807 · Cited by 31 · see citing works
Self-citationLin, R., Nie, J., Ren, J., Liang, R., Li, D., Wang, P., Gao, C., Zhuo, C., Yang, C., & Li, B. (2017) · FEBS Letters · doi:10.1002/1873-3468.12668 · Cited by 31 · see citing works
Li, W., Nagineni, C. N., Ge, H., Efiok, B. J. S., Chepelinsky, A. B., & Egwuagu, C. E. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.14.9686 · Cited by 28 · see citing works
Steimle‐Grauer, S. A., Tinguely, M., Seada, L., Fellbaum, C., & Hansmann, M. (2003) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-002-0735-5 · Cited by 29 · see citing works
Kim, S.-H., Burton, J. H., Yu, C., Sun, L., He, C., Wang, H., Morse, H. C., & Egwuagu, C. E. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500653 · Cited by 27 · see citing works
“In contrast, IRF8 is not expressed in naive T cells, but is rapidly induced in response to antigenic stimulation or TCR activation (5), suggesting that it may be required for regulating genes involved in T cell differentiation and/or effector functions.”
BackgroundResultTwo Genetic Variations in the IRF8 region are associated with Behçet’s disease in Han Chinese
Jiang, Y., Wang, H., Yu, H., Li, L., Xu, D., Hou, S., Kijlstra, A., & Yang, P. (2016) · Scientific Reports · doi:10.1038/srep19651 · Cited by 27 · see citing works
Ma, C. Y., Marioni, J. C., Griffiths, G. M., & Richard, A. C. (2020) · eLife · doi:10.7554/elife.53948 · Cited by 22 · see citing works
“Nr4a1 (Nur77) and Irf8 encode transcription factors that are rapidly expressed upon T cell activation (Moran et al., 2011; Nelson et al., 1996), and we previously found that their transcripts are upregulated at 1 and 3 hr, respectively, after strong N4 stimulation (Richard et al., 2018; Figure…”
BackgroundDeCicco-Skinner, K. L., Zolfaghari, R., Li, N., & Ross, A. C. (2000) · The Journal of Infectious Diseases · doi:10.1086/315908 · Cited by 22 · see citing works
“Two of these factors, IRF-1 and IRF-2, induce numerous antiviral genes, play roles in humoral and cell-mediated immunity [19-21], and often act as regulatory opposites, with IRF-1 activating and IRF-2 repressing the transcription of genes regulated by type I IFNs [19].”
BackgroundInterferon in chronic myeloid leukaemia: past and future
Guilhot, F., Roy, L., Saulnier, P., & Guilhot, J. (2009) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2009.10.005 · Cited by 21 · see citing works
“ICSBP is expressed mainly in haematopoietic cells [13,14].”
BackgroundTakahashi, K., Sugiyama, T., Tokoro, S., Neri, P., & Mori, H. (2011) · Cellular Immunology · doi:10.1016/j.cellimm.2011.11.004 · Cited by 21 · see citing works
Valanparambil, R. M., Tam, M., Gros, P.-P., Auger, J.-P., Segura, M., Gros, P., Jardim, A., Geary, T. G., Ozato, K., & Stevenson, M. M. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006647 · Cited by 19 · see citing works
“IRF-8 is essential for the development of various myeloid-derived cells including macrophages, dendritic cells (DC), eosinophils, and basophils, but negatively regulates neutrophil differentiation [2, 3].”
BackgroundSelf-citationBerberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis
Yang, T., Ma, X., Wang, R., et al. (2022) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2022.03.015 · Cited by 19 · see citing works
“In addition, IFN-c activator factor (GAF), as a dimer of interferon, can bind to the IFN-c activation site (GAS) and then up-regulate interferon regulatory factor 8 (IRF8) (Nelson et al., 1996).”
The development of immune-modulating compounds to disrupt HIV latency
Remoli, A. L., Marsili, G., Battistini, A., & Sgarbanti, M. (2012) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2012.05.003 · Cited by 18 · see citing works
“IRF-1 expression, which is high in activated but not in resting CD4+ T cells [57] is further enhanced by HIV-1 infection and prior to Tat expression [58].”
BackgroundSun, L., Leger, A. J. S., Yu, C., He, C., Mahdi, R. M., Chan, C., Wang, H., Morse, H. C., & Egwuagu, C. E. (2016) · PLoS ONE · doi:10.1371/journal.pone.0155420 · Cited by 18 · see citing works
“While expression of IRF8 is rapidly induced in T cells in response to TCR activation and/or cytokine stimulation, the role of IRF8 in the development or effector functions of T cells is less well understood [6].”
BackgroundHIV and Interferon Regulatory Factor 1: A Story of Manipulation and Control
Sivro, A., Su, R., Plummer, F. A., & Ball, T. B. (2013) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2013.0098 · Cited by 16 · see citing works
“This is supported by observations that latent proviruses can be reactivated by stimulating the host T cells with mitogens and anti-CD3-CD28 antibodies,(4,32,33) where both IRF1 and NF-jB are present at higher levels in activated T cells compared to resting cells.(10,34,35) Consistent with this, proinflammatory cytokin…”
Lack of Interferon Consensus Sequence Binding Protein (ICSBP) Transcripts in Human Myeloid Leukemias
Schmidt, M., Nagel, S., Proba, J., et al. (1998) · Blood · doi:10.1182/blood.v91.1.22.22_22_29 · Cited by 13 · see citing works
Dimberg, A., Kårehed, K., Nilsson, K., & Oberg, F. G. (2006) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2006.01827.x · Cited by 12 · see citing works
Qiu, Y., Zhu, Y., Yu, H., Yi, S., Su, W., Cao, Q., Yuan, G., Kijlstra, A., & Yang, P. (2017) · Oncotarget · doi:10.18632/oncotarget.17235 · Cited by 11 · see citing works
“A previous study shows that IRF8 is not expressed in naïve T cells until they are stimulated by antigens or following TCR activation, suggesting that IRF8 may be required in the process of regulating genes that are involved in T cell differentiation and/or effector functions [23].”
InfluentialMa, J., Chen, X., Xue, R., et al. (2023) · Phytotherapy Research · doi:10.1002/ptr.8016 · Cited by 9 · see citing works
“Stat-1 (Nelson et al., 1996) and AP-1 (Yukawa et al., 2020)”
Immunotherapy in Chronic Myelogenous Leukemia
Guilhot, F., Roy, L., Martineau, G., Guilhot, J., & Millot, F. (2007) · Clinical Lymphoma & Myeloma · doi:10.3816/clm.2007.s.004 · Cited by 9 · see citing works
Notake, T., Horisawa, S., Sanjo, H., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200210 · Cited by 8 · see citing works
“Ly49 gene expression, as IRF-2 was expressed comparably in IL2–expanded Ly49 and Ly49 T cells and in lymph node T cells (33), which contained many fewer Ly49 T cells than those in the”
MethodSTEM CELLS IN CHRONIC MYELOGENOUS LEUKEMIA
Verfaillie, C. M. (1997) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(05)70484-6 · Cited by 8 · see citing works
Interferon‐regulatory factors during development of CD4 and CD8 thymocytes
Simon, A. K., Desrois, M., & Schmitt‐Verhulst, A. (1997) · Immunology · doi:10.1046/j.1365-2567.1997.00271.x · Cited by 7 · see citing works
Evasion of interferon-mediated immune response by arteriviruses
Jian, Z., Ma, R., Zhu, L., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.963923 · Cited by 6 · see citing works
HIV-1 Targeting of IFN Regulatory Factors
Remoli, A. L., Marsili, G., Sgarbanti, M., Perrotti, E., Fragale, A., Orsatti, R., & Battistini, A. (2011) · Future Virology · doi:10.2217/fvl.11.125 · Cited by 6 · see citing works
Gardner, A. I., Wu, Y., Verhaegh, R., Liu, Y., Wilker, B., Soddemann, M., Keitsch, S., Edwards, M. J., Haq, I. J., Kamler, M., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100650 · Cited by 6 · see citing works
“(2021) 296 100650 The Jak/Stat pathway, which is activated by interferons, has been previously shown to stimulate expression of IRF proteins (32).”
BackgroundSun, H., Li, C. L., Lei, Y., Wang, Y., Li, B., & Ye, J. (2025) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2025.110426 · Cited by 4 · see citing works
Natural Resistance to HIV Infection: Role of Immune Activation
Naranjo‐Covo, M. M., Rincón, D. S., Flórez‐Álvarez, L., Hernández, J. C., & Zapata, W. (2025) · Immunity Inflammation and Disease · doi:10.1002/iid3.70138 · Cited by 4 · see citing works
“This could be mediated by low activation, as IRF1 seems to be highly expressed in activated cells [86].”
Schramm, K. (2016) · Elektronische Hochschulschriften der LMU München (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.20703 · Cited by 4 · see citing works
Androgen Influence on Lymphocyte Gene Expression
Bijlsma, W. R., Tonino, B. A. R., Richards, S. M., et al. (2002) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-0717-8_19 · Cited by 4 · see citing works
Interferon regulatory factor 8 induces intrinsic functional changes in mature neutrophils
Polmann, L., Grimm, J. C., Roth, J., & Barczyk‐Kahlert, K. (2025) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiaf078 · Cited by 2 · see citing works
- Authors
- Nelson, N., Kanno, Y., Hong, C., Contursi, C., Fujita, T., Fowlkes, B. J., O’Connell, E., Hu-Li, J., Paul, W. E., Jankovic, D., Sher, A. F., Coligan, J. E., Thornton, A., Appella, E., Yang, Y., & Ozato, K.
- Affiliations
- National Institutes of Health (US)
- Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development , Bethesda, MD 20892,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1996-05
- Volume
- 156
- Issue
- 10
- Pages
- 3711-3720
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1541863220
- Cited by
- 110
- References
- 0
- Citations by year
- 2026: 1 · 2025: 6 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 3 · 2017: 4 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- STAT1, T cell activation, interferon-gamma signaling, IRF1, IRF2, B cells, thymocytes, Th1/Th2 cells, transcriptional regulation, anti-CD3 stimulation, concanavalin A
- MeSH terms
- Interferon Regulatory Factor-8, Amino Acid Sequence, Animals, Antibodies, Monoclonal, B-Lymphocytes, Base Sequence, Carrier Proteins, Cell Differentiation, Cell Line, DNA-Binding Proteins, Hybridomas, Interferon-gamma, Interphase, Lipopolysaccharides, Lymphocyte Activation, Molecular Sequence Data, Phosphoproteins, Receptors, Antigen, T-Cell, Repressor Proteins, T-Lymphocytes, Trans-Activators, CD3 Complex, Th1 Cells, Th2 Cells, STAT1 Transcription Factor, Interferon Regulatory Factors, Interferon Regulatory Factor-1, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
