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Kiyoshi Hirahara Publications

I) Original paper

  1. 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).
  2. 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).
  3. 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).
  4. 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).
  5. 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).
  6. 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).
  7. 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).
  8. 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).
  9. 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).
  10. 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).
  11. 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).
  12. 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).
  13. 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).
  14. 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).
  15. 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).
  16. 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).
  17. 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).
  18. 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).
  19. 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).
  20. 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).
  21. 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).
  22. 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).
  23. 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).
  24. 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).
  25. 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).
  26. 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).
  27. 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).
  28. 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).
  29. 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).
  30. 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).
  31. 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).
  32. 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).
  33. 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).
  34. Shinoda, K., Hirahara, K., and Nakayama, T.: Maintenance of pathogenic Th2 cells in allergic disorders. Allergol. Int. 66:369-376 (2017). (3.194)
  35. 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).
  36. 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).
  37. 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).
  38. 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).
  39. 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).
  40. 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).
  41. 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).
  42. 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. in press.

II) Review Article and Book Chapter

  1. 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).
  2. 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).
  3. 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).
  4. 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).
  5. Hirahara, K., and Nakayama, T.: CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int. Immunol. 28:163-171 (2016).
  6. Eberle F. C., Bruck, J., Holstein, J., Hirahara, K., and Ghoreschi, K.: Recent advances in understanding psoriasis. F1000Res F1000 Faculty Rev-770 (2016).
  7. 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).
  8. 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).
  9. 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).
  10. 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).
  11. 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).
  12. 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).

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