
Member
Kiyoshi Hirahara Publications
I) Original paper
- Nigo, Y. I., Yamashita, M., Hirahara, K., Shinnakasu, R., Inami, M., Kimura, M., Hasegawa, A., Kohno, Y., and Nakayama, T.: Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function. Proc. Natl. Acad. Sci. USA 103:2286-2291 (2006).
- Yamashita, M., Hirahara, K., Shinnakasu, R., Hosokawa, H., Norikane, S., Kimura, M. Y., Hasegawa, A., and Nakayama, T.: Crucial role of MLL for the maintenance of memory T helper type 2 cell responses. Immunity 24:611-622 (2006).
- Yamashita, M., Kuwahara, M., Suzuki, A., Hirahara, K., Shinnakasu, R., Hosokawa, H., Hasegawa, A., Motohashi, S., Iwama, A., and Nakayama, T.: Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene. J. Exp. Med. 205:1109-1120 (2008).
- Hirahara, K., Yamashita, M., Iwamura, C., Shinoda, K., Hasegawa, A., Yoshizawa, H., Koseki, H., Gejyo, F., and Nakayama, T.: Repressor of GATA regulates TH2-driven allergic airway inflammation and airway hyperresponsiveness. J. Allergy Clin. Immunol. 122:512-520.e11 (2008).
- Hirahara, K., Ghoreschi, K., Laurence, A., Yang, X. P., Kanno, Y., and O'Shea, J. J.: Signal transduction pathways and transcriptional regulation in Th17 cell differentiation. Cytokine Growth Factor Rev. 21:425-434 (2010).
- Ghoreschi, K., Laurence, A., Yang, X. P., Hirahara, K., and O'Shea, J. J.: T helper 17 cell heterogeneity and pathogenicity in autoimmune disease. Trends Immunol. 32:395-401 (2011).
- Yang, X. P., Ghoreschi, K., Steward-Tharp, S. M., Rodriguez-Canales, J., Zhu, J., Grainger, J. R., Hirahara, K., Sun, H. W., Wei, L., Vahedi, G., Kanno, Y., O'Shea, J. J., and Laurence, A.: Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat. Immunol. 12:247-254 (2011).
- Hirahara, K., Vahedi, G., Ghoreschi, K., Yang, X. P., Nakayamada, S., Kanno, Y., O'Shea, J. J., and Laurence, A.: Helper T-cell differentiation and plasticity: insights from epigenetics. Immunology 134:235-245 (2011).
- Kanno, Y., Vahedi, G., Hirahara, K., Singleton, K.,and O'Shea, J. J.: Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticity. Annu. Rev. Immunol. 30:707-731 (2012).
- Laurence, A., Ghoreschi, K., Hirahara, K., Yang, X. P., and O'Shea, J. J.: Therapeutic inhibition of the Janus kinases. Inflammation and Regeneration 32:16-22 (2012).
- Takahashi, H., Kanno, T., Nakayamada, S., Hirahara, K., Sciumè, G., Muljo, S. A., Kuchen, S., Casellas, R., Wei, L., Kanno, Y., and O'Shea, J. J.: TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nat. Immunol. 13:587-595 (2012).
- Hirahara, K., Ghoreschi, K., Yang, X. P., Takahashi, H., Laurence, A., Vahedi, G., Sciumè, G., Hall, A. O., Dupont, C. D., Francisco, L. M., Chen, Q., Tanaka, M., Kanno, Y., Sun, H. W., Sharpe, A. H., Hunter, C. A., and O'Shea, J. J.: Interleukin-27 priming of T cells controls Interleukin-17 production in trans via induction of the ligand PD-L1. Immunity 36:1017-1030 (2012).
- Sciumè, G., Hirahara, K., Takahashi, H., Laurence, A., Villarino, A. V., Singleton, K. L., Spencer, S. P., Wilhelm, C., Poholek, A. C., Vahedi, G., Kanno, Y., Belkaid, Y., and O'Shea, J. J.: Distinct requirements for T-bet in gut innate lymphoid cells. J. Exp. Med. 209:2331-2338 (2012).
- Vahedi, G., C. Poholek, A., Hand, T. W., Laurence, A., Kanno, Y., O'Shea, J. J., and Hirahara, K.: Helper T-cell identity and evolution of differential transcriptomes and epigenomes. Immunol. Rev. 252:24-40 (2013).
- Hirahara, K., Poholek, A., Vahedi, G., Laurence, A., Kanno, Y., Milner, J. D., and O'Shea, J. J.: Mechanisms underlying helper T-cell plasticity: Implications for immune-mediated disease. J. Allergy Clin. Immunol. 131:1276-1287 (2013).
- Roychoudhuri, R.*, Hirahara, K.*, Mousavi, K.*, Clever, D., Klebanoff, C. A., Bonelli, M., Sciumè, G., Zare, H., Vahedi, G., Dema, B., Yu, Z., Liu, H., Takahashi, H., Rao, M., Muranski, P., Crompton, J. G., Punkosdy, G., Bedognetti, D., Wang, E., Hoffmann, V., Rivera, J., Marincola, F. M., Nakamura, A., Sartorelli, V., Kanno, Y., Gattinoni, L., Muto, A., Igarashi, K., O'Shea, J. J., and Restifo, N. P.: BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis. *These authors are contributed equally to this work. Nature 498:506-510 (2013).
- Hosokawa, H., Tanaka, T., Kato, M., Shinoda, K., Tohyama, H., Hanazawa, A., Tamaki, Y., Hirahara, K., Yagi, R., Sakikawa, I., Morita, A., Nagira, M., Poyurovsky, M. V., Suzuki, Y., Motohashi, S., and Nakayama, T.: Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression. Proc. Natl. Acad. Sci. USA 110:18626-18631 (2013).
- Nakayamada, S., Poholek, A. C., Lu, K. T., Takahashi, H., Kato, M., Iwata, S., Hirahara, K., Cannons, J. L., Schwartzberg, P. L., Vahedi, G., Sun, H. W., Kanno, Y., and O'Shea, J. J.: Type I IFN induces binding of STAT1 to Bcl6: divergent roles of STAT family transcription factors in the T follicular helper cell genetic program. J. Immunol. 192:2156-2166 (2014).
- Steward-Tharp, S. M., Laurence, A., Kanno, Y., Kotlyar, A., Villarino, A. V., Sciume, G., Kuchen, S., Resch, W., Wohlfert, E. A., Jiang, K., Hirahara, K., Vahedi, G., Sun, H. W., Feigenbaum, L., Milner, J. D., Holland, S. M., Casellas, R., Powrie, F., and O'Shea, J. J.: A mouse model of HIES reveals pro and anti-inflammatory functions of STAT3. Blood 123:2978-2987 (2014).
- Watanabe, Y., Onodera, A., Kanai, U., Ichikawa, T., Obata-Ninomiya, K., Wada, T., Kiuchi, M., Iwamura, C., Tumes, D. J., Shinoda, K., Yagi, R., Motohashi, S., Hirahara, K., and Nakayama, T.: Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells. Proc. Natl. Acad. Sci. USA 111:12829-12834 (2014).
- Endo, Y., Hirahara, K., Iinuma, T., Shinoda, K., Tumes, D. J., Asou, H. K., Matsugae, N., Obata-Ninomiya, K., Yamamoto, H., Motohashi, S., Oboki, K., Nakae, S., Saito, H., Okamoto, Y., and Nakayama, T.: The Interleukin-33-p38 kinase axis confers memory T helper 2 cell pathogenicity in the airway. Immunity 42:294-308 (2015).
- Iinuma, T., Okamoto, Y., Yamamoto, H., Inamine-Sasaki, A., Ohki, Y., Sakurai, T., Funakoshi, U., Yonekura, S., Sakurai, D., Hirahara, K., and Nakayama, T.: Interleukin-25 and mucosal T cells in noneosinophilic and eosinophilic chronic rhinosinusitis. Ann. Allergy Asthma Immunol. 114:289-298 (2015).
- Hirahara, K., Onodera, A., Villario, A. V., Bonelli, M., Sciume, G., Laurence, A., Sun, H. W., Brooks, S. R., Vahedi, G., Shih, H. Y., Gtierrez-Cruz, G., Iwata, S., Suzuki, R., Mikami, Y., Okamoto, Y., Nakayama, T., Holland, S. M., Hunter, C. A., Kanno, Y., and O'Shea, J. J.: Asymmetric action of STAT transcription factors drives transcriptional outputs and cytokine specificity. Immunity 42:877-889 (2015).
- Yang, X. P., Jiang, K., Hirahara, K., Vahedi, G., Afzali, B., Sciume, G., Boneli, M., Sun, H. W., Jankovic, D., Kanno, Y., Sartorelli, V., O'Shea, J. J., and Laurence, A.: EZH2 is crucial for both differentiation of regulatory T cells and T effector cell expansion. Sci. Rep. 5:10643 (2015).
- Endo, Y., Asou, H. K., Matsugae, N., Hirahara, K., Shinoda, K., Tumes, D. J., Tokuyama, H., Yokote, K., and Nakayama, T.: Obesity drives Th17 cell differentiation by inducing the lipid metabolic kinase, ACC1. Cell Rep. 12:1042-1055 (2015).
- Onodera, A., Tumes, D. J., Watanabe, Y., Hirahara, K., Kaneda, A., Sugiyama, F., Suzuki, Y., and Nakayama, T.: Spatial interplay between Polycomb and Trithorax complexes controls transcriptional activity in T lymphocytes. Mol. Cell. Biol. 35:3841-3853 (2015).
- Bonelli, M., Goschl, L., Bluml, S., Karonitsch, T., Hirahara, K., Ferner, E., Steiner, C. W., Steiner, G., Smolen, J. S., and Scheinecker, C.: Abatacept (CTLA-4Ig) treatment reduces T cell apoptosis and regulatory T cell suppression in patients with rheumatoid arthritis. Rheumatology 55:710-720 (2016).
- Jain, R., Chen, Y., Kanno, Y., Joyce-Shaikh, B., Vahedi, G., Hirahara, K., Blumenschein, W. M., Sukumar, S., Haines, C. J., Sadekova, S., McClanahan, T. K., McGeachy, M. J., O'Shea, J. J., and Cua, D. J.: Interleukin-23-induced transcription factor Blimp-1 promotes pathogenicity of T helper 17 cells. Immunity 44:131-142 (2016).
- Shinoda, K., Hirahara, K., Iinuma, T., Ichikawa, T., Suzuki, A. S., Sugaya, K., Tumes, D. J., Yamamoto, H., Hara, T., Tani-ichi, S., Ikuta, K., Okamoto, Y., and Nakayama, T.: Thy1+IL-7+ lymphatic endthelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation. Proc. Natl. Acad. Sci. USA 113:E2842-51 (2016).
- Hirahara, K., Schwartz, D., Gadina, M., Kanno, Y., and O'Shea, J. J.: Targeting cytokine signaling in autoimmunity: back to the future and beyond. Curr. Opin. Immunol. 43:89-97 (2016).
- Hayashizaki, K.,* Kimura, M. Y.,* Tokoyoda, K.,* Hosokawa, H., Shinoda, K., Hirahara, K., Ichikawa, T., Onodera, A., Hanazawa, A., Iwamura, C., Kakuta, J., Muramoto, K., Motohashi, S., Tumes, D. J., Iinuma, T., Yamamoto, H., Ikehara, Y., Okamoto, Y., and Nakayama, T.: Myosin light chain 9 and 12 are functional ligands for CD69 that regulate airway inflammation. (*these authors contributed equally to this work) Sci. Immunol. 1:pp.eaaf9154 (2016).
- Brück, J., Holstein, J., Glocova, I., Seidel, U., Geisel, J., Kanno, T., Kumagai, J., Mato, N., Sudowe, S., Widmaier, K., Sinnberg, T., Yazdi, A. S., Eberle, F. C., Hirahara, K., Nakayama, T., Röcken, M., and Ghoreschi, K.: Nutritional control of IL-23/Th17-mediated autoimmune disease through HO-1/STAT3 activation. Sci. Rep. 7:44482 (2017).
- Iwata, S., Mikami, Y., Sun, H.-W., Brooks, S. R., Jankovic, D., Hirahara, K., Onodera, A., Shih, H.-Y., Kawabe, T., Jiang, K., Nakayama, T., Sher, A., O'Shea, J. J., Davis, F. P., and Kanno, Y.: The transcription factor T-bet limits amplification of type I IFN transcriptome and circuitry in T helper 1 cells. Immunity 46:983-991 (2017).
- Shinoda, K., Hirahara, K., and Nakayama, T.: Maintenance of pathogenic Th2 cells in allergic disorders. Allergol. Int. 66:369-376 (2017). (3.194)
- Onodera, A., Kiuchi, M., Kokubo, K., Kato, M., Ogino, T., Horiuchi, S., Kanai, U., Hirahara, K., and Nakayama, T.: Menin controls the memory Th2 cell function by maintaining the epigenetic integrity of Th2 cells. J. Immunol. 199:1153-1162 (2017).
- Mato, N., Hirahara, K., Ichikawa, T., Kumagai, J., Nakayama, M., Yamasawa, H., Bando, M., Hagiwara, K., Sugiyama, Y., and Nakayama, T.: Memory-type ST2+CD4+ T cells participate in the steroid-resistant pathology of eosinophilic pneumonia. Sci. Rep. 7:6805 (2017).
- Ito, T., Hirahara, K., Onodera, A., Koyama-Nasu, R., Yano, I., and Nakayama, T.: Anti-tumor immunity via the superoxide-eosinophil axis induced by a lipophilic component of Mycobacterium lipomannan. Int. Immunol. 29:411-421 (2017).
- Morimoto, Y., Hirahara, K., Kiuchi, M., Wada, T., Ichikawa, T., Kanno, T., Okano, M., Kokubo, K., Onodera, A., Sakurai, D., Okamoto, Y., and Nakayama, T.: Amphiregulin-producing pathogenic memory T helper-2 cells instruct eosinophils to secrete Osteopontin and facilitate airway fibrosis. Immunity 49:134-150 (2018).
- Obata-Ninomiya, K., Ishiwata, K., Nakano, H., Endo, Y., Ichikawa, T., Onodera, A., Hirahara, K., Okamoto, Y., Kanuka, H., and Nakayama, T.: CXCR6+ST2+ memory Th2 cells induced the expression of major basic protein in eosinophils to reduce the fecundity of helminth. Proc. Natl. Acad. Sci. USA 115:E9849-E9858 (2018).
- Yamamoto, T., Endo, Y., Onodera, A., Hirahara, K., Asou, H. K., Nakajima, T., Kanno, T., Ouchi, Y., Uematsu, S., Nishimasu, H., Nureki, O., Tumes, D. J., Shimojo, N., and Nakayama, T.: DUSP10 constrains IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells. Nat. Commun. 9:4231 (2018).
- Wada, T., Hirahara, K., Aoki, A., Morimoto, Y., Kiuchi, M., Kumagai, J., Okano, M., Kokubo, K., Kato, M., Fukano, C., Ohashi-Doi, K., and Nakayama, T.: An Optimized protocol for the analysis of house dust mite (Dermatophagoides farinae)-induced neutrophil-dominant airway inflammation. J. Immunol. Methods 465:53-60 (2019).
- Tumes, D., Hirahara, K., Papadopoulos, M., Shinoda, K., Onodera, A., Kumagai, J., Yip, K. H., Pant, H., Kokubo, K., Kiuchi, M., Aoki, A., Obata-Ninomiya, K., Tokoyoda, K., Endo, Y., Kimura, M. Y., and Nakayama, T.: Ezh2 controls development of natural killer T cells, which cause spontaneous asthma-like pathology. J. Allergy Clin. Immunol. 144(2):549-560.e10 (2019).
- Ichikawa, T.*, Hirahara, K.*, Kokubo, K.*, Kiuchi, M., Aoki, A., Morimoto, Y., Kumagai, J., Onodera, A., Mato, N., Tumes, D. J., Goto, Y., Hagiwara, K., Inagaki, Y., Sparwasser, T., Tobe, K., and Nakayama, T.: CD103hi Treg cells constrain lung fibrosis induced by CD103lo tissue-resident pathogenic CD4 T cells. (*these authors contributed equally to this work) Nat. Immunol. 20:1469-1480 (2019).
- Göschl, L., Preglej, T., Boucheron, N., Saferding, V., Müller, L., Platzer, A., Hirahara, K., Shih, H. Y., Backlund, J., Matthias, P., Niederreiter, B., Hladik, A., Kugler, M., Gualdoni, G. A., Scheinecker, C., Knapp, S., Seiser, C., Holmdahl, R., Tillmann, K., Plasenzotti, R., Podesser, B., Aletaha, D., Smolen, J. S., Karonitsch, T., Steiner, G., Ellmeier, W., and Bonelli, M.: Histone Deacetylase 1 (HDAC1): A key player of T cell-mediated arthritis. J. Autoimmun. 108:102379 (2020).
- Aoki, T., Takami, M., Takatani, T., Motoyoshi, K., Ishii, A., Hara, A., Toyoda, T., Okada, R., Hino, M., Koyama-Nasu, R., Kiuchi, M., Hirahara, K., Kimura, M. Y., Nakayama, T., Shimojo, N., and Motohashi, S.: Activated invariant natural killer T cells directly recognize leukemia cells in CD1d-independent manner. Cancer Sci. 111(7):2223-2233 (2020).
- Suzuki, A. S., Yagi, R., Kimura, M., Iwamura, C., Shinoda, K., Onodera, A., Hirahara, K., Tumes, D. J., Koyama-Nasu, R., Iismaa, S. E., Graham, R. M., Motohashi, S., and Nakayama, T.: Essential role for CD30-Transglutaminase 2 axis in memory Th1 and Th17 cell generation. Front. Immunol. 11:1536 (2020).
- Sciumè, G., Mikami, Y., Jankovic, D., Nagashima, H., Villarino, A. V., Morrison, T., Yao, C., Signorella, S., Sun, H. W., Brooks, S. R., Fang, D., Sartorelli, V., Nakayamada, S., Hirahara, K., Zitti, B., Davis, F. P., Kanno, Y., O'Shea, J. J., and Shih, H. Y.: Rapid enhancer remodeling and transcription factor repurposing enable high magnitude gene induction upon acute activation of NK cells. Immunity 53:745-758 (2020).
- Kiuchi, M., Onodera, A., Kokubo, K., Ichikawa, T., Morimoto, Y., Kawakami, E., Takayama, N., Eto, K., Koseki, H., Hirahara, K., and Nakayama, T.: The Cxxc1 subunit of the Trithorax complex directs epigenetic licensing of CD4+ T cell differentiation. J. Exp. Med. 218(4):e20201690 (2021).
- Takasato, Y., Kurashima, Y., Kiuchi, M., Hirahara, K., Murasaki, S., Arai, F., Izawa, K., Kaitani, A., Shimada, K., Saito, Y., Toyoshima, S., Nakamura, M., Fujisawa, K., Okayama, Y., Kunishima, J., Kubo, M., Takemura, N., Uematsu, S., Akira, S., Kitaura, J., Takahashi, T., Nakayama, T., and Kiyono, H.: Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy. Mucosal Immunol. 14(3):640-651 (2021).
II) Review Article and Book Chapter
- Villarino, A., Yang, X. P., Hirahara, K., Kanno, Y., O'Shea, J. J., and Laurence, A.: Function of JAKs and STATs in lymphocyte: bench to bedside. Springer-Verlag Wien Thomas Decker (Ed.) (2012).
- Endo, Y., Hirahara, K., Yagi, R., Tumes, D. J., and Nakayama, T.: Pathogenic memory type Th2 cells in allergic inflammation. Trends Immunol. 35:69-78 (2014).
- Bonelli, M., Shih, H. Y., Hirahara, K., Singelton, K., Laurence, A., Poholek, A., Hand, T., Mikami, Y., Vahedi, G., Kanno, Y., and O'Shea, J. J.: Helper T cell plasticity: impact of extrinsic and intrinsicsSignals on transcriptomes and epigenomes. Curr. Top. Microbiol. Immunol. 381:279-326 (2014).
- Shih, H. Y., Sciume, G., Poholek, A. C., Vahedi, G., Hirahara, K., Villarino, A. V., Bonelli, M., Bosselut, R., Kanno, Y., Muljo, S. A., and O'Shea, J. J.: Transcriptional and epigenetic networks of helper T and innate lymphoid cells. Immunol. Rev. 261:23-49 (2014).
- Hirahara, K., and Nakayama, T.: CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int. Immunol. 28:163-171 (2016).
- Eberle F. C., Bruck, J., Holstein, J., Hirahara, K., and Ghoreschi, K.: Recent advances in understanding psoriasis. F1000Res F1000 Faculty Rev-770 (2016).
- Nakayama, T., Hirahara, K., Onodera, A., Endo, Y., Hosokawa, H., Shinoda, K., Tumes, D. J., and Okamoto, Y.: Th2 Cells in Health and Disease. Annu. Rev. Immunol. 35:53-84 (2017).
- Tumes, D. J., Papadopoulos, M., Endo, Y., Onodera, A., Hirahara, K., and Nakayama, T.: Epigenetic regulation of T-helper cell differentiation, memory, and plasticity in allergic asthma. Immunol. Rev. 278:8-19 (2017).
- Hirahara, K., Mato, N., Hagiwara, K., and Nakayama, T.: The pathogenicity of IL-33 on steroid-resistant eosinophilic inflammation via the activation of memory-type ST2+CD4+ T cells. J. Leukoc. Biol. 104:895-901 (2018).
- Hirahara, K., Shinoda, K., Endo, Y., Ichikawa, T., and Nakayama, T.: Maintenance of memory-type pathogenic Th2 cells in the pathophysiology of chronic inflammation. Inflamm. Regen. 38:10 (2018).
- Hirahara, K., Shinoda, K., Morimoto, Y., Kiuchi, M., Aoki, A., Kumagai, J., Kokubo, K., and Nakayama, T.: Immune cell-epithelial/mesenchymal interaction contributing to allergic airway inflammation associated pathology. Front. Immunol. 10:570 (2019).
- Hirahara, K., Aoki, A., Morimoto, Y., Kiuchi, M., Okano, M., and Nakayama, T.: The immunopathology of lung fibrosis: amphiregulin-producing pathogenic memory T helper-2 cells control the airway fibrotic responses by inducing eosinophils to secrete osteopontin. Semin. Immunopathol. 41(3):339-348 (2019).
- Hirahara, K., and Nakayama, T.: Induction and regulation of mucosal memory T cell response. Mucosal Vaccines (Second Edition) 133-142 (2019).
- Aoki, A., Hirahara, K., Kiuchi, M., and Nakayama, T.: Eosinophils: Cells known for over 140 years with broad and new functions. Allergol. Int. 70(1):3-8 (2021).
- Hirahara, K., Aoki, A., and Nakayama, T.: Pathogenic helper T cells. Allergol. Int. 70(2):169-173 (2021).
- Hirahara, K., Kokubo, K., Aoki, A., Kiuchi, M., and Nakayama, T.: The role of CD4+ resident memory T cells in local immunity in the mucosal tissue - protection versus pathology -. Front. Immunol. 12:616309 (2021).
- Hirahara, K., Aoki, A., Kiuchi, M., and Nakayama, T.: Memory-type pathogenic TH2 cells and ILC2s in type 2 allergic inflammation. J. Allergy Clin. Immunol. 147(6):2063-2066 (2021).
- Nakayama, T., Hirahara, K., Kimura, M. Y., Iwamura, C., Kiuchi, M., Kokubo, K., Onodera, A., Hashimoto, K., and Motohashi, S.: CD4+ T cells in inflammatory diseases: pathogenic T-helper cells and the CD69-Myl9 system. Int. Immunol. in press.
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