The Menin–Bach2 axis is critical for regulating CD4 T-cell senescence and cytokine homeostasis
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Although CD4 T-cell senescence plays an important role in immunosenescence, the mechanism behind this process remains unclear. Here we show that T cell-specific Menin deficiency results in the premature senescence of CD4 T cells, which is accompanied by the senescence-associated secretory phenotype after antigenic stimulation and dysregulated cytokine production. Menin is required for the expansion and survival of antigen-stimulated CD4 T cells in vivo and acts by targeting Bach2, which is known to regulate immune homeostasis and cytokine production. Menin binds to the Bach2 locus and controls its expression through maintenance of histone acetylation. Menin binding at the Bach2 locus and the Bach2 expression are decreased in the senescent CD4 T cells. These findings reveal a critical role of the Menin-Bach2 pathway in regulating CD4 T-cell senescence and cytokine homeostasis, thus indicating the involvement of this pathway in the inhibition of immunosenescence. Immunosenescence particularly affects the T-cell compartment and is involved in the age-related decline of immune functions. Here, the authors show that the absence of the tumour suppressor Menin results in premature senescence of CD4 T cells.
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DRISR closest to ATAC-UP regions were significantly enriched (q-value < 0.05) in 43 motifs, including NF-κB, Jun-AP1, Batch2, Stat3, HIF-1α, and CTCF.
“The results indicated that the DRISR closest to ATAC-UP regions were significantly enriched (q-value < 0.05) in 43 motifs (Fig. 2F), including NF-κB (35), Jun-AP1 (36), Batch2 (37), Stat3, HIF-1α, and CTCF (11, 21), which are known to be involved in cellular senescence or inflammatory SASP gene expression.”
From Chromatin conformational changes at human satellite II contribute to the senescence phenotype in the tumor microenvironment (2023) · cites this paper as [37]
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Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358 · see citing works
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038 · see citing works
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,016 · see citing works
CONSENSUS: Guidelines for Diagnosis and Therapy of MEN Type 1 and Type 2
Brandi, M. L., Gagel, R. F., Angeli, A., Bilezikian, J. P., Beck‐Peccoz, P., Bordi, C., Conte‐Devolx, B., Falchetti, A., Gheri, R. G., Libroia, A., et al. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.12.8070 · Cited by 2,010 · see citing works
Cellular senescence and the senescent secretory phenotype: therapeutic opportunities
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64098 · Cited by 1,774 · see citing works
Induction by Antigen of Intrathymic Apoptosis of CD4 + CD8 + TCR lo Thymocytes in Vivo
MURPHY, K. M. M., Heimberger, A. B., & Loh, D. Y. (1990) · Science · doi:10.1126/science.2125367 · Cited by 1,714 · see citing works
Inflammatory networks during cellular senescence: causes and consequences.
Freund, A., Orjalo, A. V., Desprez, P.-Y., & Campisi, J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.03.003 · Cited by 1,354 · see citing works
Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,175 · see citing works
Chien, Y., Scuoppo, C., Wang, X., Fang, X., Balgley, B., Bolden, J. E., Premsrirut, P., Luo, W., Chicas, A., Lee, C. S., et al. (2011) · Genes & Development · doi:10.1101/gad.17276711 · Cited by 1,046 · see citing works
Multiple common variants for celiac disease influencing immune gene expression
Dubois, P. C. A., Trynka, G., Franke, L., Hunt, K. A., Romanos, J., Curtotti, A., Zhernakova, A., Heap, G., Ádány, R., Aromaa, A. J., et al. (2010) · Nature Genetics · doi:10.1038/ng.543 · Cited by 1,010 · see citing works
Gavazzi, G., & Krause, K.-H. (2002) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(02)00437-1 · Cited by 990 · see citing works
The common biology of cancer and ageing
Finkel, T., Serrano, M., & Blasco, M. A. (2007) · Nature · doi:10.1038/nature05985 · Cited by 988 · see citing works
Stress-activated cap’n’collar transcription factors in aging and human disease
Sykiotis, G. P., & Bohmann, D. (2010) · Science Signaling · doi:10.1126/scisignal.3112re3 · Cited by 776 · see citing works
Yokoyama, A., Somervaille, T. C. P., Smith, K. S., Rozenblatt–Rosen, O., Meyerson, M. M., & Cleary, M. L. (2005) · Cell · doi:10.1016/j.cell.2005.09.025 · Cited by 698 · see citing works
(2014) · Fordham University Press eBooks · doi:10.2307/j.ctt9qdsck.5 · Cited by 679 · see citing works
Yokoyama, A., Wang, Z., Wysocka, J., Sanyal, M., Aufiero, D. J., Kitabayashi, I., Herr, W., & Cleary, M. L. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.13.5639-5649.2004 · Cited by 654 · see citing works
Menin Associates with a Trithorax Family Histone Methyltransferase Complex and with the Hoxc8 Locus
Hughes, C. M., Rozenblatt–Rosen, O., Milne, T. A., Copeland, T. D., Levine, S. S., Lee, J. C., Hayes, D. N., Shanmugam, K. S., Bhattacharjee, A., Biondi, C., et al. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00081-4 · Cited by 641 · see citing works
Senescent cells as a source of inflammatory factors for tumor progression
Davalos, A. R., Coppe, J.-P., Campisi, J., & Desprez, P.-Y. (2010) · Cancer and Metastasis Reviews · doi:10.1007/s10555-010-9220-9 · Cited by 636 · see citing works
Menin Critically Links MLL Proteins with LEDGF on Cancer-Associated Target Genes
Yokoyama, A., & Cleary, M. L. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.003 · Cited by 551 · see citing works
Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci
Cooper, J. D., Smyth, D. J., Smiles, A. M., Plagnol, V., Walker, N. M., Allen, J. E., Downes, K., Barrett, J. C., Healy, B. C., Mychaleckyj, J. C., et al. (2008) · Nature Genetics · doi:10.1038/ng.249 · Cited by 529 · see citing works
Motif module map reveals enforcement of aging by continual NF-κB activity
Adler, A. S., Sinha, S., Kawahara, T. L. A., Zhang, J. Y., Segal, E., & Chang, H. Y. (2007) · Genes & Development · doi:10.1101/gad.1588507 · Cited by 466 · see citing works
NF-κB inhibition delays DNA damage–induced senescence and aging in mice
Tilstra, J. S., Robinson, A. R., Wang, J., Gregg, S. Q., Clauson, C. L., Reay, D. P., Nasto, L. A., St Croix, C. M., Usas, A., Vo, N., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci45785 · Cited by 462 · see citing works
Trithorax group proteins: switching genes on and keeping them active
Schuettengruber, B., Martinez, A., Iovino, N., & Cavalli, G. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3230 · Cited by 454 · see citing works
BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis
Roychoudhuri, R., Hirahara, K., Mousavi, K., Clever, D. C., Klebanoff, C. A., Bonelli, M. M., Sciumè, G., Zare, H., Vahedi, G., Dema, B., et al. (2013) · Nature · doi:10.1038/nature12199 · Cited by 412 · see citing works
Healing and Hurting: Molecular Mechanisms, Functions, and Pathologies of Cellular Senescence
Adams, P. D. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.021 · Cited by 326 · see citing works
The transcriptional programme of antibody class switching involves the repressor Bach2
Muto, A., Tashiro, S., Nakajima, O., Hoshino, H., Takahashi, S., Sakoda, E., Ikebe, D., Yamamoto, M. P., & Igarashi, K. (2004) · Nature · doi:10.1038/nature02596 · Cited by 292 · see citing works
Osorio, F. G., Bárcena, C., Soria-Valles, C., Ramsay, A. J., de Carlos, F., Cobo, J., Fueyo, A., Freije, J. M. P., & López-Otín, C. (2012) · Genes & Development · doi:10.1101/gad.197954.112 · Cited by 276 · see citing works
Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis
Scacheri, P. C., Davis, S. R., Odom, D. T., Crawford, G. E., Perkins, S., Halawi, M. J., Agarwal, S. K., Marx, S. J., Spiegel, A. M., Meltzer, P. S., et al. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020051 · Cited by 218 · see citing works
Kometani, K., Nakagawa, R., Shinnakasu, R., Kaji, T., Rybouchkin, A., Moriyama, S., Furukawa, K., Koseki, H., Takemori, T., & Kurosaki, T. (2013) · Immunity · doi:10.1016/j.immuni.2013.06.011 · Cited by 217 · see citing works
Self-citationBach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch
Muto, A., Ochiai, K., Kimura, Y., Itoh‐Nakadai, A., Calame, K. L., Ikebe, D., Tashiro, S., & Igarashi, K. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.257 · Cited by 210 · see citing works
T-cell immunosenescence: lessons learned from mouse models of aging
Maue, A. C., Yager, E. J., Swain, S. L., Woodland, D. L., Blackman, M. A., & Haynes, L. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.04.007 · Cited by 182 · see citing works
Chen, Y.-X., Yan, J., Keeshan, K., Tubbs, A., Wang, H., Silva, A., Brown, E. J., Hess, J. L., Pear, W. S., & Hua, X. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510347103 · Cited by 176 · see citing works
Bach2 maintains T cells in a naive state by suppressing effector memory-related genes
Tsukumo, S.-I., Unno, M., Muto, A., Takeuchi, A., Kometani, K., Kurosaki, T., Igarashi, K., & Saito, T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1306691110 · Cited by 168 · see citing works
Self-citationMenin and its interacting proteins: elucidation of menin function
Balogh, K., Rácz, K., Patócs, A., & Hunyady, L. (2006) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2006.09.004 · Cited by 141 · see citing works
Shimatani, K., Nakashima, Y., Hattori, M., Hamazaki, Y., & Minato, N. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908805106 · Cited by 134 · see citing works
van Gisbergen, K. P. J. M., Klarenbeek, P. L., Kragten, N. A. M., Unger, P. A., Nieuwenhuis, M. B. B., Wensveen, F. M., ten Brinke, A., Tak, P. P., Eldering, E., Nolte, M. A., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.04.020 · Cited by 133 · see citing works
Hu, G., & Chen, J. (2013) · Nature Communications · doi:10.1038/ncomms3830 · Cited by 132 · see citing works
Rheumatoid Arthritis: A Role for Immunosenescence?
Lindström, T. M., & Robinson, W. H. (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2010.02965.x · Cited by 122 · see citing works
Roles and mechanisms of cellular senescence in regulation of tissue homeostasis
Ohtani, N., & Hara, E. (2013) · Cancer Science · doi:10.1111/cas.12118 · Cited by 120 · see citing works
Christodoulou, K., Wiskin, A. E., Gibson, J., Tapper, W., Willis, C., Afzal, N. A., Upstill‐Goddard, R., Holloway, J. W., Simpson, M. A., Beattie, R. M., et al. (2012) · Gut · doi:10.1136/gutjnl-2011-301833 · Cited by 120 · see citing works
Jin, S., Zhao, H., Yi, Y., Nakata, Y., Kalota, A., & Gewirtz, A. M. (2010) · Journal of Clinical Investigation · doi:10.1172/jci38030 · Cited by 120 · see citing works
La, P., Desmond, A., Hou, Z., Silva, A. C., Schnepp, R. W., & Hua, X. (2006) · Oncogene · doi:10.1038/sj.onc.1209400 · Cited by 112 · see citing works
Bach1 inhibits oxidative stress–induced cellular senescence by impeding p53 function on chromatin
Dohi, Y., Ikura, T., Hoshikawa, Y., Katoh, Y., Ota, K., Nakanome, A., Muto, A., Omura, S., Ohta, T., Ito, A., et al. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1516 · Cited by 104 · see citing works
Onodera, A., Yamashita, M., Endo, Y., Kuwahara, M., Tofukuji, S., Hosokawa, H., Kanai, A., Suzuki, Y., & Nakayama, T. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20100760 · Cited by 100 · see citing works
Self-citationChronic inflammation and aging: DNA damage tips the balance
Cavanagh, M. M., Weyand, C. M., & Goronzy, J. J. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.04.003 · Cited by 99 · see citing works
Molecular Mechanisms Involved in the Aging of the T-cell Immune Response
Moro‐García, M. A., Alonso‐Arias, R., & López‐Larrea, C. (2012) · Current Genomics · doi:10.2174/138920212803759749 · Cited by 85 · see citing works
Granzymes in age-related cardiovascular and pulmonary diseases
Hendel, A., Hiebert, P., Boivin, W. A., Williams, S. J., & Granville, D. J. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.5 · Cited by 78 · see citing works
Gao, S.-B., Feng, Z.-J., Xu, B., Wu, Y., Yin, P., Yang, Y., Hua, X., & Jin, G.-H. (2009) · Oncogene · doi:10.1038/onc.2009.273 · Cited by 69 · see citing works
Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells
Li, B. E., Gan, T., Meyerson, M. M., Rabbitts, T. H., & Ernst, P. (2013) · Blood · doi:10.1182/blood-2013-03-486647 · Cited by 67 · see citing works
Aged-related shifts in T cell homeostasis lead to intrinsic T cell defects
Haynes, L., & Swain, S. L. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.001 · Cited by 66 · see citing works
Menin regulates the function of hematopoietic stem cells and lymphoid progenitors
Maillard, I. P., Chen, Y.-X., Friedman, A. D., Yang, Y., Tubbs, A., Shestova, O. E., Pear, W. S., & Hua, X. (2008) · Blood · doi:10.1182/blood-2008-01-135012 · Cited by 53 · see citing works
Menin represses tumorigenesis via repressing cell proliferation.
Wu, T., & Hua, X. (2011) · Europe PMC (PubMed Central) · Cited by 48 · see citing works
Menin dynamics and functional insight: Take your partners
Balogh, K., Patócs, A., Hunyady, L., & Rácz, K. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.04.011 · Cited by 46 · see citing works
The Expansion and Maintenance of Antigen‐Selected CD8+ T Cell Clones
Fearon, D. T. (2007) · Advances in immunology · doi:10.1016/s0065-2776(07)96003-4 · Cited by 34 · see citing works
Age-related Deficiencies in Antigen-Specific CD4 T cell Responses: Lessons from Mouse Models.
Haynes, L., & Lefebvre, J. S. (2011) · Europe PMC (PubMed Central) · Cited by 33 · see citing works
Williams, V., Quintin, P. S., & Hoadley, S. (2006) · Action Research · doi:10.1177/1476750306066803 · Cited by 18 · see citing works
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Wagner, T. A., McLaughlin, S., Garg, K., Cheung, C. Y. K., Larsen, B. B., Styrchak, S., Huang, H. C., Edlefsen, P. T., Mullins, J. I., & Frenkel, L. M. (2014) · Science · doi:10.1126/science.1256304 · Cited by 677 · see citing works
Tumour burden and efficacy of immune-checkpoint inhibitors
Dall’Olio, F. G., Marabelle, A., Caramella, C., Garcia, C., Aldea, M., Chaput, N., Robert, C., & Besse, B. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00564-3 · Cited by 350 · see citing works
Immune System Dysfunction in the Elderly
Eduardo Fuentes, Q., FUENTES, M., Alarcón, M. A., & Palomo, I. F. (2017) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765201720160487 · Cited by 234 · see citing works
BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency
Afzali, B., Grönholm, J., Vandrovcová, J., O'Brien, C., Sun, H., Vanderleyden, I., Davis, F. P., Khoder, A., Zhang, Y., Hegazy, A. N., et al. (2017) · Nature Immunology · doi:10.1038/ni.3753 · Cited by 151 · see citing works
EZH2 is crucial for both differentiation of regulatory T cells and T effector cell expansion
Yang, X., Jiang, K., Hirahara, K., Vahedi, G., Afzali, B., Sciumè, G., Bonelli, M. M., Sun, H., Jankovic, D. L., Kanno, Y., et al. (2015) · Scientific Reports · doi:10.1038/srep10643 · Cited by 150 · see citing works
Epigenetic Regulation of Cellular Senescence and Aging
Sidler, C. L., Kovalchuk, O., & Kovalchuk, I. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00138 · Cited by 147 · see citing works
SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation
Yu, X., Lao, Y., Teng, X.-L., Li, S., Zhou, Y., Wang, F., Guo, X., Deng, S., Chang, Y., Wu, X., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05676-6 · Cited by 146 · see citing works
BACH transcription factors in innate and adaptive immunity
Igarashi, K., Kurosaki, T., & Roychoudhuri, R. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.26 · Cited by 130 · see citing works
Self-citationImmunology of the ageing kidney
Sato, Y., & Yanagita, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0185-9 · Cited by 126 · see citing works
The Bach Family of Transcription Factors: A Comprehensive Review
Zhou, Y. X., Wu, H., Zhao, M., Chang, C., & Lu, Q. (2016) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-016-8538-7 · Cited by 126 · see citing works
Physiology and pathology of T-cell aging
Minato, N., Hattori, M., & Hamazaki, Y. (2020) · International Immunology · doi:10.1093/intimm/dxaa006 · Cited by 121 · see citing works
The impact of senescence-associated T cells on immunosenescence and age-related disorders
Fukushima, Y., Minato, N., & Hattori, M. (2018) · Inflammation and Regeneration · doi:10.1186/s41232-018-0082-9 · Cited by 118 · see citing works
Senescent cells and macrophages: key players for regeneration?
Elder, S. S., & Emmerson, E. (2020) · Open Biology · doi:10.1098/rsob.200309 · Cited by 109 · see citing works
Cesana, D., de Sio, F. R. S., Rudilosso, L., Gallina, P., Calabria, A., Beretta, S., Merelli, I., Bruzzesi, E., Passerini, L., Nozza, S., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00609-1 · Cited by 107 · see citing works
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Jasiulionis, M. G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00197 · Cited by 99 · see citing works
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Kuwahara, M., Ise, W., Ochi, M., Suzuki, J., Kometani, K., Maruyama, S., Izumoto, M., Matsumoto, A., Takemori, N., Takemori, A., et al. (2016) · Nature Communications · doi:10.1038/ncomms12596 · Cited by 98 · see citing works
Self-citationOrchestration of plasma cell differentiation by Bach2 and its gene regulatory network
Igarashi, K., Ochiai, K., Itoh‐Nakadai, A., & Muto, A. (2014) · Immunological Reviews · doi:10.1111/imr.12201 · Cited by 93 · see citing works
Suzuki, J., Yamada, T., Inoue, K., Nabe, S., Kuwahara, M., Takemori, N., Takemori, A., Matsuda, S., Kanoh, M., Imai, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05854-6 · Cited by 87 · see citing works
Self-citationTanaka, H., Muto, A., Shima, H., Katoh, Y., Sax, N., Tajima, S., Brydun, A., Ikura, T., Yoshizawa-Sugata, N., Masai, H., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.713842 · Cited by 80 · see citing works
Richer, M. J., Lang, M. L., & Butler, N. S. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600847 · Cited by 77 · see citing works
Epigenomic drivers of immune dysfunction in aging
Keenan, C. R., & Allan, R. S. (2018) · Aging Cell · doi:10.1111/acel.12878 · Cited by 76 · see citing works
Grant, F. M., Yang, J., Nasrallah, R., Clarke, J. D., Sadiyah, F., Whiteside, S. K., Imianowski, C. J., Kuo, P., Vardaka, P., Todorov, T. Z., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190711 · Cited by 71 · see citing works
Self-citationXiong, Y., Xiong, Y., Zhang, H., Zhao, Y., Han, K., Zhang, J., Zhao, D., Yu, Z., Geng, Z., Wang, L., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.780897 · Cited by 69 · see citing works
Challenges and strategies for the eradication of the HIV reservoir
Kimata, J. T., Rice, A. P., & Wang, J. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.05.015 · Cited by 62 · see citing works
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Jiang, Y., Cao, S., Gao, L., Wang, Y., Zhou, B., Hu, X., Pu, Y., Li, Z.-L., Wang, Q., Xiao, X., et al. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2018.5647 · Cited by 43 · see citing works
Klasić, M., Markulin, D., Vojta, A., Samaržija, I., Biruš, I., Dobrinić, P., Ventham, N. T., Trbojević‐Akmačić, I., Šimurina, M., Štambuk, J., et al. (2018) · Clinical Epigenetics · doi:10.1186/s13148-018-0507-y · Cited by 41 · see citing works
Ando, R., Shima, H., Tamahara, T., Sato, Y., Watanabe‐Matsui, M., Kato, H., Sax, N., Motohashi, H., Taguchi, K., Yamamoto, M. P., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.661702 · Cited by 41 · see citing works
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Lu, Y., Ruan, Y., Pan, H., Rui, K., Liu, Q., Wang, S., & Cui, D. (2022) · Clinical Immunology · doi:10.1016/j.clim.2022.109202 · Cited by 39 · see citing works
Tamahara, T., Ochiai, K., Muto, A., Kato, Y., Sax, N., Matsumoto, M., Koseki, T., & Igarashi, K. (2017) · Molecular and Cellular Biology · doi:10.1128/mcb.00418-17 · Cited by 38 · see citing works
Ikegami, K., Yamashita, M., Suzuki, M., Nakamura, T., Hashimoto, K., Kitagaki, J., Yanagita, M., Kitamura, M., & Murakami, S. (2023) · Aging · doi:10.18632/aging.204569 · Cited by 36 · see citing works
Self-citationThe role of HIV integration in viral persistence: no more whistling past the proviral graveyard
Maldarelli, F. M. (2016) · Journal of Clinical Investigation · doi:10.1172/jci80564 · Cited by 36 · see citing works
Profiles of Long Noncoding RNAs in Human Naive and Memory T Cells
Spurlock, C. F., Shaginurova, G. I., Tossberg, J. T., Hester, J., Chapman, N. S., Guo, Y. P., Crooke, P. S., & Aune, T. M. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700232 · Cited by 36 · see citing works
Liu, M., Deng, W., Tang, L., Liu, M., Bao, H., Guo, C., Zhang, C. X., Lu, J., Wang, H., Lu, Z., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28657-2 · Cited by 35 · see citing works
Zhou, Y., Li, G. Y., Ren, J. P., Wang, L., Zhao, J., Ning, S., Zhang, Y., Lian, J. Q., Huang, C. X., Jia, Z., et al. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.5a0316-119rr · Cited by 34 · see citing works
Miura, Y., Morooka, M., Sax, N., Roychoudhuri, R., Itoh‐Nakadai, A., Brydun, A., Funayama, R., Nakayama, K., Satomi, S., Matsumoto, M., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1601863 · Cited by 31 · see citing works
Bach2 regulates autophagy to modulate UVA-induced photoaging in skin fibroblasts
Wang, M., Lei, M., Chang, L., Yang, X., Guo, Y., Pourzand, C., Bartsch, J. W., Chen, J., Luo, J., Karisma, V. W., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.04.003 · Cited by 31 · see citing works
Mullins, J. I., & Frenkel, L. M. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiw636 · Cited by 29 · see citing works
Xiong, Y., WANG, Y., Zhang, J., Zhao, N., Zhang, A., Zhang, A., Zhao, D., Yu, Z., Yin, Y., Song, L., et al. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01993-0 · Cited by 29 · see citing works
Epigenetics of T cells regulated by Polycomb/Trithorax molecules
Onodera, A., & Nakayama, T. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.03.001 · Cited by 27 · see citing works
Self-citationOuyang, M., Su, W., Xiao, L., Rao, J. N., Jiang, L., Li, Y., Turner, D. J., Gorospe, M., & Wang, J. (2014) · Biochemical Journal · doi:10.1042/bj20141028 · Cited by 25 · see citing works
RetractedSenescent CD8 + T cells acquire NK cell‐like innate functions to promote antitumor immunity
Kakuda, T., Suzuki, J., Matsuoka, Y., Kikugawa, T., Saika, T., & Yamashita, M. (2023) · Cancer Science · doi:10.1111/cas.15824 · Cited by 24 · see citing works
Self-citationKiuchi, M., Onodera, A., Kokubo, K., Ichikawa, T., Morimoto, Y., Kawakami, E., Takayama, N., Eto, K., Koseki, H., Hirahara, K., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20201690 · Cited by 22 · see citing works
Self-citationMeta-epigenetic shifts in T cell aging and aging-related dysfunction
Rousseau, L., Hajdu, K. L., & Ho, P. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01146-6 · Cited by 21 · see citing works
Siddiqui, S., Lustig, A., Carter, A., Sankar, M., Daimon, C. M., Premont, R. T., Etienne, H., van Gastel, J., Azmi, A., Janssens, J., et al. (2017) · Aging · doi:10.18632/aging.101185 · Cited by 21 · see citing works
Margolis, D. M., & Bushman, F. D. (2014) · Science · doi:10.1126/science.1257426 · Cited by 21 · see citing works
Probiotic Consumption Boosts Thymus in Obesity and Senescence Mouse Models
Balcells, M. F., Monteros, M. J. M., Gómez, A. L., Cazorla, S. I., Perdigón, G., & Maldonado-Galdeano, C. (2022) · Nutrients · doi:10.3390/nu14030616 · Cited by 20 · see citing works
The critical role of Bach2 in regulating type 2 chronic airway inflammation
Yamashita, M., & Kuwahara, M. (2018) · International Immunology · doi:10.1093/intimm/dxy020 · Cited by 19 · see citing works
Self-citationJiang, X., Cao, M., Wu, J., Wang, X., Zhang, G., Yang, C., Gao, P., & Zou, Y. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.971424 · Cited by 18 · see citing works
Menin Controls the Memory Th2 Cell Function by Maintaining the Epigenetic Integrity of Th2 Cells
Onodera, A., Kiuchi, M., Kokubo, K., Kato, M., Ogino, T., Horiuchi, S., Kanai, U., Hirahara, K., & Nakayama, T. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1602129 · Cited by 18 · see citing works
Self-citationEbina‐Shibuya, R., Matsumoto, M., Kuwahara, M., Jang, K., Sugai, M., Ito, Y., Funayama, R., Nakayama, K., Sato, Y., Ishii, N., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.808535 · Cited by 18 · see citing works
Self-citationThe role of Bach2 in regulating CD8 + T cell development and function
Weng, X., Zheng, M., Liu, Y., & Lou, G. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01551-8 · Cited by 17 · see citing works
Xu, Y., Wang, Z., Li, S., Su, J., Gao, L., Ou, J., Lin, Z., Luo, O. J., Xiao, C., & Chen, G. (2024) · Science China Life Sciences · doi:10.1007/s11427-024-2695-x · Cited by 17 · see citing works
Maldarelli, F. M. (2015) · Journal of Virus Eradication · doi:10.1016/s2055-6640(20)30930-4 · Cited by 16 · see citing works
A CRISPR/Cas9-mediated screen identifies determinants of early plasma cell differentiation
Xiong, E., Popp, O., Salomon, C., Mertins, P., Kocks, C., Rajewsky, K., & Chu, V. T. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1083119 · Cited by 15 · see citing works
Senescent T Cells in Age-Related Diseases
Yu, P.-J., Zhou, M. L., Liu, Y., & Du, J. (2024) · Aging and Disease · doi:10.14336/ad.2024.0219 · Cited by 15 · see citing works
Cellular senescence by loss of Men1 in osteoblasts is critical for age‐related osteoporosis
Ukon, Y., Kaito, T., Hirai, H., Kitahara, T., Bun, M., Kodama, J., Tateiwa, D., Nakagawa, S., Ikuta, M., Furuichi, T., et al. (2024) · Aging Cell · doi:10.1111/acel.14254 · Cited by 15 · see citing works
Self-citationA Review of the Scaffold Protein Menin and its Role in Hepatobiliary Pathology
Ehrlich, L., Hall, C. M., Meng, F., Lairmore, T. C., Alpini, G. D., & Glaser, S. S. (2017) · Gene Expression · doi:10.3727/105221617x695744 · Cited by 15 · see citing works
Characteristics and mechanisms of T‐cell senescence: A potential target for cancer immunotherapy
Wu, H., Li, J., Zhang, Z., & Zhang, Y. (2024) · European Journal of Immunology · doi:10.1002/eji.202451093 · Cited by 14 · see citing works
Senescence-associated T cells in immunosenescence and diseases
Fukushima, Y., Ueno, R., Minato, N., & Hattori, M. (2024) · International Immunology · doi:10.1093/intimm/dxae056 · Cited by 14 · see citing works
Zhang, K., Chen, C., Liu, Y., Chen, H., & Liu, J. (2014) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12328 · Cited by 14 · see citing works
Miyata, K., Zhou, X., Nishio, M., Hanyu, A., Chiba, M., Kawasaki, H., Osako, T., Takeuchi, K., Ohno, S., Ueno, T., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2305046120 · Cited by 13 · see citing works
Duan, S., Sawyer, T. W., Witten, B. L., Song, H., Else, T., & Merchant, J. L. (2024) · The Journal of Pathology · doi:10.1002/path.6241 · Cited by 13 · see citing works
Low-level PDT treatment modulated photoaging mediated by UVA irradiation through regulating Bach2
Wang, M., Yang, X., Chang, L., Chen, J., Luo, J., Wu, Y. L., Lei, X., & Li, Z. (2019) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2019.101606 · Cited by 13 · see citing works
Bach2 in CD4+ T cells from SLE patients modulates B‐cell differentiation and IgG production
Long, D., Yang, B., Yang, M., Xiong, F., Zhu, X., Tan, Y., & Wu, H. (2023) · European Journal of Immunology · doi:10.1002/eji.202250109 · Cited by 13 · see citing works
Yamada, T., Kanoh, M., Nabe, S., Yasuoka, T., Suzuki, J., Matsumoto, A., Kuwahara, M., Maruyama, S., Fujimoto, T., Sakisuka, R., et al. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502295 · Cited by 13 · see citing works
Self-citationA BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn's Disease
Laffin, M., Fedorak, R. N., Wine, E., Dicken, B. J., & Madsen, K. L. (2018) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2018.01.052 · Cited by 12 · see citing works
Bevington, S. L., Fiancette, R., Gajdasik, D. W., Keane, P., Soley, J. K., Willis, C., Coleman, D. J. L., Withers, D. R., & Cockerill, P. N. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.642807 · Cited by 11 · see citing works
Zheng, Y., Lu, Y., Huang, X., Li, H., Chen, Z., Zhou, B., Ma, Y., Xie, G., Yang, J., Bian, B., et al. (2019) · European Journal of Immunology · doi:10.1002/eji.201948320 · Cited by 11 · see citing works
Yu, M., Liu, J., Shi, W., Jiang, M., Hou, H., Xue, Y., Xu, H., Jiang, L., Liu, H., Cheng, D., et al. (2025) · The FASEB Journal · doi:10.1096/fj.202503324r · Cited by 10 · see citing works
MEN1 deficiency stabilizes PD‐L1 and promotes tumor immune evasion of lung cancer
Zhang, C., Sun, N., Fei, Q.-Z., Peng, L., Wei, C., Liu, X., Miao, S., Chai, M., Wang, F., Wang, D., et al. (2024) · Cancer Science · doi:10.1111/cas.16196 · Cited by 8 · see citing works
Higher-Order Chromatin Regulation of Inflammatory Gene Expression
Xu, J.-W., Ling, S., & Liu, J. (2017) · Mediators of Inflammation · doi:10.1155/2017/7848591 · Cited by 8 · see citing works
BACH2 drives the development and function of group 2 innate lymphoid cells
Liu, G., Wang, Y., Yi, X., Wang, J., Zhang, J., Feng, X., Wang, H., Chen, C., Liu, Q., Wang, J., et al. (2025) · Science Advances · doi:10.1126/sciadv.ads4323 · Cited by 6 · see citing works
Bach2 Controls Homeostasis of Eosinophils by Restricting the Type-2 Helper Function of T Cells
Sato, Y., Kato, H., Ebina‐Shibuya, R., Itoh‐Nakadai, A., Okuyama, R., & Igarashi, K. (2017) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.241.175 · Cited by 6 · see citing works
Thompson, M. J., Hogg, P., Paoli, A. D., & Burgess, J. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz231 · Cited by 5 · see citing works
A case report of multiple endocrine neoplasia type 1 and autoimmune disease
Chaves, C., da Silva, T. N., Pereira, B. D., Anselmo, J., Claro, I., Cavaco, B. M., Saramago, A., & Leite, V. (2021) · Medicine · doi:10.1097/md.0000000000028145 · Cited by 5 · see citing works
Wen, J., Lagler, T. M., Sun, Q., Yang, Y., Chen, J., Harigaya, Y., Sankaran, V. G., Hu, M., Reiner, A. P., Raffield, L. M., et al. (2022) · PLoS Genetics · doi:10.1371/journal.pgen.1009984 · Cited by 5 · see citing works
A role of Achaete-scute complex homolog 2 in T follicular regulatory cell development
Iida, K., Suga, K., Suzuki, K., Kurihara, S., Yabe, Y., Kageyama, T., Meguro, K., Tanaka, S., Iwata, A., Suto, A., et al. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.04.065 · Cited by 4 · see citing works
Regulation of the Immune System in Aging: Focus on Epigenetic Mechanisms
Айтбаев, К. А., Murkamilov, I. T., Абдилалимовна, М. Ж., Kudaibergenova, I., & Yusupov, F. A. (2022) · The Russian Archives of Internal Medicine · doi:10.20514/2226-6704-2022-12-1-35-44 · Cited by 3 · see citing works
Harnessing Stem Cell-Like Memory T Cells for Adoptive Cell Transfer Therapy of Cancer
Lugli, E., & Gattinoni, L. (2015) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-3-319-21167-1_8 · Cited by 3 · see citing works
LI, J., Sanui, T., Shida, M., Yotsumoto, K., Ahmad, M., Wang, Z., Xiao, M., Hayashi, C., Shinjo, T., Taketomi, T., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1806138 · Cited by 2 · see citing works
Roles of Menin in T cell differentiation and function: Current knowledge and perspectives
Zhou, P., Liu, W., & Ma, J. (2024) · Immunology · doi:10.1111/imm.13837 · Cited by 1 · see citing works
Dysregulation of the tumor suppressor Menin and its target Bach2 in HTLV-1 infection
Sejima, H., Naito, T., Fukushima, T., & Saito, M. (2025) · Retrovirology · doi:10.1186/s12977-025-00660-7 · Cited by 1 · see citing works
Cuc, B. T., Tong, Y., Wu, Z., Álvarez-Simón, D., & Fillatreau, S. (2026) · Immunological Reviews · doi:10.1111/imr.70180 · Cited by 1 · see citing works
EPIGENETIC ALTERATIONS IN GENE EXPRESSION IN THE AGING IMMUNE SYSTEM
Miteva, D., & Velikova, T. V. (2023) · Anti-Aging Eastern Europe · doi:10.56543/aaeeu.2023.2.1.05 · Cited by 1 · see citing works
Yamashita, M., Kuwahara, M., Suzuki, J., & Yamada, T. (2016) · Springer eBooks · doi:10.1007/978-4-431-56068-5_32
Self-citationFactors associated with the post-operative recurrence of Crohn's disease
Laffin, M. (2018) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3rn30p5r
Isogawa, M., Shinoda, M., Kotaki, R., Terahara, K., Onodera, T., Kabasawa, K., Toyama‐Kousaka, M., Fujisawa, M., Watanabe, M., Tonouchi, K., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115934
Xiong, Y., WANG, Y., Zhang, J., Zhao, N., Zhang, H., Zhang, A., Zhao, D., Yu, Z., Yin, Y., Song, L., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13192471
The MLL1–MENIN complex preserves CD8 T cell memory through a TOX–BTLA-TCF1 axisPreprint
Chiu, B. C. (2026) · Research Square · doi:10.21203/rs.3.rs-9268813/v1
Takagi, K., Suzuki, J., Matsuoka, Y., Kuwahara, M., Oshikiri, T., & Yamashita, M. (2026) · Cancer Science · doi:10.1111/cas.70439
Self-citationGheitasi, R., Rezaei, M., Fard, P. N., Roel, D., Baumgart, S., Dudziak, D., Rose, N., Petzinna, S. M., Kamradt, T., Watzl, C., et al. (2026) · npj Aging · doi:10.1038/s41514-026-00491-6
Ikegami, K. (n.d.) · Institutional Repositories DataBase (IRDB) · doi:10.18910/56128
Sharma, A. A., Dropathi, M., Sadek, N., Li, D., Hoh, R., Rutishauser, R. L., Pillai, S. K., Sereti, I., Chomont, N., Deeks, S. G., et al. (2026) · medRxiv · doi:10.64898/2026.09.11.26362694
- Authors
- Kuwahara, M., Suzuki, J., Tofukuji, S., Yamada, T., Kanoh, M., Matsumoto, A., Maruyama, S., Kometani, K., Kurosaki, T., Ohara, O., Nakayama, T., & Yamashita, M.
- Affiliations
- Ehime University Hospital (JP)
- Kazusa DNA Research Institute (JP)
- Ehime University (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Chiba University (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Yamashita, Masakatsu
- ORCID
- Venue
- Nature Communications
- Published
- 2014-04-02
- Volume
- 5
- Issue
- 1
- Pages
- 3555-3555
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3988815
- OpenAlex
- W2053013356
- Cited by
- 98
- References
- 56
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 6 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 5 · 2014: 5
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Naito Foundation
- Astellas Pharma
- Astellas Foundation for Research on Metabolic Disorders
- Kanae Foundation for the Promotion of Medical Science
- Japan Society for the Promotion of Science (25118718, 25860376, 21229007, 24659475, 25670232, 26221305, 23390075, 26460579)
- Precursory Research for Embryonic Science and Technology
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- menin, BACH2, immunosenescence, senescence-associated secretory phenotype, cytokine homeostasis, histone acetylation, T cell survival, antigen stimulation, tumour suppressor, T cell homeostasis
- MeSH terms
- Animals, Female, Homeostasis, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Proto-Oncogene Proteins, CD4-Positive T-Lymphocytes, Cytokines, Cellular Senescence, Mice, Knockout, Basic-Leucine Zipper Transcription Factors
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