京都大学 ウイルス・再生医科学研究所 免疫制御分野
生田研究室 Ikuta Laboratory
Institute for Frontier Life and Medical Sciences



  1. 2018
  2. 2017
  3. 2016
  4. 2015
  5. 2014
  6. 2013
  7. 2012
  8. 2011
  9. 2010
  10. 2009
  11. 2008
  12. 2007
  13. 2006
  14. 2005
  15. 2004
  16. 2003
  17. 2002
  18. 2001
  19. 2000


  • Baumann, N., Torti, N., Welten, S. P. M., Barnstorf, I., Borsa, M., Pallmer, K., Oduro, J. D., Cicin-Sain, L., Ikuta, K., Ludewig, B., and Oxenius, A. (2018). Tissue maintenance of CMV-specific inflationary memory T cells by IL-15. PLos Pathogen, 14(4): e1006993.
  • Shimba, A., Cui, G., Tani-ichi, S., Ogawa, M., Abe, S., Okazaki, F., Kitano, S., Miyachi, H., Yamada, H., Hara, T., Yoshikai, Y., Nagasawa, T., Schütz, G., and Ikuta, K. (2018). Glucocorticoids drive diurnal oscillations in T cell distribution and responses by inducing interleukin-7 receptor and CXCR4. Immunity, 48: 286-298.

    強い免疫抑制作用を持つグルココルチコイドが、IL-7受容体とケモカイン受容体CXCR4の発現を誘導することで、T細胞の体内分布を制御し、T細胞の免疫応答能を高めることを明らかにした。生体内のグルココルチコイドがT細胞の免疫機能を高める働きをもつこと、内分泌系が免疫系を直接制御すること、免疫機能が日内変動することが示された。大阪大学長澤丘司教授、九州大学吉開泰信教授、ドイツがん研究センターGünther Schütz教授らとの共同研究である。


  • Nakamizo, S., Honda, T., Adachi, A., Nagatake, T., Kunisawa, J., Kitoh, A., Otsuka, A., Dainichi, T., Nomura, T., Ginhoux, F., Ikuta, K., Egawa, G., and Kabashima, K. (2017).High fat diet exacerbates murine psoriatic dermatitis by increasing the number of IL-17-producing γδ T cells. Sci. Rep., 7: 14076.


  • Gomes, A. C.*, Hara, T.*†, Lim, V. Y.*, Herndler-Brandstetter, D., Nevius, E., Sugiyama, T., Tani-ichi, S., Schlenner, S., Richie, E., Rodewald, H., Flavell, R. A., Nagasawa, T., Ikuta, K., and Pereira, J. P.† (2016). Hematopoietic stem cell niches produce lineage-instructive signals to control multipotent progenitor differentiation. Immunity, 45: 1219-1231. *Co-first author. †corresponding author.


  • Gil-Cruz, C., Perez-Shibayama, C., Onder, L., Chai, Q., Cupovic, J., Cheng, H., Novkovic, M., Lang, P. A., Geuking, M. B., McCoy, K. D., Abe, S., Cui, G., Ikuta, K., Scandella, E., and Ludewig, B. (2016). Fibroblastic reticular cells regulate intestinal inflammation through IL-15-mediated control of group 1 ILCs. Nat. Immunol., 17: 1388-1396.
  • 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. (2016). Thy-1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation. Proc. Natl. Acad. Sci. USA., 113 (20): E2842-2851.
  • Terashima, A., Okamoto, K., Nakashima, T., Akira, S., Ikuta, K. and Takayanagi, H. (2016). Sepsis-induced osteoblast ablation causes immunodeficiency. Immunity, 44: 1434-1443.
  • Huang, Y., Getahun, A., Heiser, R. A., Detanico, T. O., Kirchenbaum, G. A., Casper, T. L., Huang, C., Aydintug, M. K., Carding, S. R., Ikuta, K., Huang, H., Wysocki, L. J., Cambier, J. C., O'Brien, R. L., and Born, W. K. (2016). γδ T cells shape pre-immune peripheral B cell populations. J. Immunol., 196: 217-231.


  • Nishijima, H., Kitano, S., Miyachi, H., Morimoto, J., Kawano, H., Hirota, F., Morita, R., Mouri, Y., Masuda, K., Imoto, I., Ikuta, K., and Matsumoto, M. (2015). Ectopic Aire expression in the thymic cortex reveals inherent properties of Aire as a tolerogenic factor within the medulla. J. Immunol., 195: 4641-4649.
  • Adachi, T., Kobayashi, T., Sugihara, E., Yamada, T., Ikuta, K., Pittaluga, S., Saya, H., Amagai, M., and Nagao, K. (2015). Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma. Nat. Med., 21: 1272-1279.
  • Abe, A., Tani-ichi, S., Shitara, S., Cui, G., Yamada, H., Miyachi, H., Kitano, S., Hara, T., Abe, R., Yoshikai, Y., and Ikuta, K. (2015). An enhancer of the IL-7 receptor α-chain locus controls IL-7 receptor expression and maintenance of peripheral T cells. J. Immunol., 195: 3129-3138.


  • Wagatsuma, K.*, Tani-ichi, S.*, Liang, B., Shitara, S., Ishihara, K., Abe, M., Miyachi, H., Kitano, S., Hara, T., Nanno, M., Ishikawa, H., Sakimura, K., Nakano, M., Kimura, H., and Ikuta, K. (2015). STAT5 orchestrates local epigenetic changes for chromatin accessibility and rearrangements by direct binding to the TCRγ locus. J. Immunol., 195: 1804-1814. *equal contribution.

    TCRγ遺伝子座のJγ1プロモーターを含む940bpのDNA領域を欠失したマウスとJγ1プロモーターの3つのSTATモチーフに点突然変異を導入したマウスを作製し、STAT5がJγプロモーターに結合することが局所的なクロマチンのアクセシビリティとJγ1/ Eγクロマチンループ形成を誘導することで、TCRγ遺伝子座の組換えを引き起こすことを明らかにした。ヤクルト中央研究所・南野昌信博士、石川博通博士、新潟大学脳研究所・崎村建司教授、熊本大学・中尾光善教授、東京工業大学生命理工学研究科・木村宏教授との共同研究である。

  • Alp, Ö. S., Durlanik, S., Schulz, D., McGrath, M., Grün, J. R., Bardua, M., Ikuta, K., Sgouroudis, E., Riedel, R., Zehentmeier, S., Hauser, A. E., Tsuneto, M., Melchers, F., Tokoyoda, K., Chang, H-D., Thiel, A., and Radbruch, A. (2015). Memory CD8+ T cells colocalize with IL-7+ stromal cells in bone marrow and rest in terms of proliferation and transcription. Eur. J. Immunol., 45: 975-987.
  • Huang, Y., Heiser, R. A., Detanico, T. O., Getahun, A., Kirchenbaum, G. A., Aydintug, M. K., Smith, C. W., Carding, S. R., Ikuta, K., Huang, H., Wysocki, L. J., Cambier, J. C., O'Brien, R. L., and Born, W. K. (2015). γδ T cells affect IL-4 production and B cell tolerance. Proc. Natl. Acad. Sci. USA., 112(1):E39-48.
  • Nakamura, M., Shibata, K., Hatano, S., Sato, T., Ohkawa, Y., Yamada, H., Ikuta, K., and Yoshikai, Y. (2015). A genome-wide analysis identifies a Notch-RBP-Jκ-IL-7Rα axis that controls IL-17-producing γδ T cell homeostasis in mice. J. Immunol., 194: 243-251.


  • Tsuneto, M., Kajikhina, E., Seiler, K., Reimer, A., Tornack, J., Bouquet, C., Simmons, S., Knoll, M., Wolf, I., Tokoyoda, K., Hauser, A., Hara, T., Tani-ichi, S., Ikuta, K., Grun, J. R., Grutzkau, A., Engels, N., Wienands, J., Yanagisawa, Y., Ohnishi, K., and Melchers, F. (2014). Environments of B cell development. Immunol. Lett., 157:60-63, 2014.
  • Cui, G., Hara, T., Simmons, S., Wagatsuma, K., Abe, A., Miyachi, H., Kitano, S., Ishii, M., Tani-ichi, S., and Ikuta, K. (2014). Characterization of the interleukin-15 niche in primary and secondary lymphoid organs in vivo. Proc. Natl. Acad. Sci. USA., 111:1915-1920.

    IL-15-CFPノックインマウスを作製し、IL-15産生細胞を蛍光タンパク質CFPで可視化した。骨髄の間葉系ストローマ細胞、胸腺髄質の上皮細胞、血管内皮細胞、リンパ節の線維芽細胞様細網細胞などでIL-15が産生されており、IL-15とIL-7の産生細胞は大きく異なることを示した。大阪大学医学研究科・石井優教授、Szandor Simmons博士との共同研究である。


  • Tani-ichi, S., Shimba, A., Wagatsuma, K., Miyachi, H., Kitano, S., Imai, K., Hara, T., and Ikuta, K. (2013). The interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations. Proc. Natl. Acad. Sci. USA., 110:612-617.
  • Sekai, M., Tani-ichi, S., Yoneyama, M., Fujita, T., Kina, T., and Ikuta, K. (2013). Lymphocyte-stromal cell interaction induces IL-7 expression by interferon regulatory factors. Mol. Immunol., 54:378-385.
  • Shitara, S., Hara, T., Liang, B., Wagatsuma, K., Zuklys, S., Hollander, G. A., Nakase, H., Chiba, T., Tani-ichi, S., and Ikuta, K. (2013). Interleukin-7 produced by thymic epithelial cells plays a major role in the development of thymocytes and TCRγδ+ intraepithelial lymphocytes. J. Immunol., 190:6173-6179.
  • Lee, J. K., Won, C., Yi, E. H., Seok, S. H., Kim, M. H., Kim, S. J., Chung, M. H., Lee, H. G., Ikuta., K., and Ye, S. K. (2013). Signal transducer and activator of transcription 3 (Stat3) contributes to T-cell homeostasis by regulating pro-survival Bcl-2 family genes. Immunol., 140:288-300.
  • Hanazawa, A., Hayashizaki, K., Shinoda, K., Yagita, H., Okumura, K., Lohning, M., Hara, T., Tani-ichi, S., Ikuta., K., Eckes, B., Radbruch, A., Tokoyoda, K., and Nakayama, T. (2013). CD49b-dependent establishment of T helper cell memory. Immunol. Cell Biol., 91:524-531.
  • Tsuneto, M., Tokoyoda, K., Kajikhina, E., Hauser, A. E., Hara, T., Tani-ichi, S., Ikuta., K., and Melchers, F. (2013).
    B cell progenitors and precursors change their microenvironment in fetal liver during early development. Stem Cells, 31:2800-2812.


  • Hara, T., Shitara, S., Imai, K., Miyachi, H., Kitano, S., Yao, H., Tani-ichi, S., and Ikuta, K. (2012). Identification of interleukin-7-producing cells in primary and secondary lymphoid organs using IL-7-GFP knock-in mice. J. Immunol., 189:1577-1584.
  • Liang, B., Hara, T., Wagatsuma, K., Zhang, J., Maki, K., Miyachi, H., Kitano, S., Yabe-Nishimura, C., Tani-ichi, S., and Ikuta, K. (2012). Role of hepatocyte-derived IL-7 in maintenance of intrahepatic NK T and T cells and development of B cells in fetal liver. J. Immunol., 189:4444-4450.


  • Shinohara, T., Nemoto, Y., Kanai, T., Kameyama, K., Okamoto, R., Tsuchiya, K., Nakamura, T., Totsuka, T., Ikuta, K., and Watanabe, M. (2011). Upregulated IL-7Rα expression on colitogenic memory CD4+ T cells may participate in the development and persistence of chronic colitis. J. Immunol., 186:2623-2632.
  • Ma, Y., Aymeric, L., Locher, C., Mattarollo, S. R., Delahaye, N. F., Pereira, P., Boucontet, L., Apetoh, L., Ghiringhelli, F., Casares, N., Lasarte, J. J., Matsuzaki, G., Ikuta, K., Ryffel, B., Benlagha, K., Tesniere, A., Ibrahim, N., Dechanet-Merville, J., Chaput, N., Smyth, M. J., Kroemer, G., and Zitvogel, L. (2011). Contribution of IL-17-producing γδ T cells to the efficacy of anticancer chemotherapy. J. Exp. Med., 208:491-503.
  • Tani-ichi, S., Satake, M., and Ikuta, K. (2011). The pre-TCR signal induces transcriptional silencing of the TCRγ locus by reducing the recruitment of STAT5 and Runx to transcriptional enhancers. Int. Immunol., 23:553-563.


  • Yoshida, Y.O., Umemura, M., Yahagi, A., O'Brien, R. L., Ikuta, K., Kishihara, K., Hara, H., Nakae, S., Iwakura, Y., and Matsuzaki, G. (2010). Essential role of interleukin-17A in the formation of a mycobacterial infection-induced granuloma in the lung. J. Immunol., 184:4414-4422.
  • Tani-ichi, S., Lee, H.-C., Ye, S.-K., and Ikuta, K. (2010). Accessibility control of TCR Vγ region by STAT5. Int. Immunol., 22:693-703.


  • Tokuriki, A., Iyoda, T., Inaba, K., Ikuta, K., Fujimoto, S., Kumakiri, M., and Yokota, Y. (2009). Dual role for Id2 in chemical carcinogen-induced skin tumorigenesis. Carcinogenesis, 30:1645-1650.
  • Tani-ichi, S., Satake, M., and Ikuta, K. (2009). Activation of the mouse T cell receptor γ enhancers by STAT5. Int. Immunol., 21:1079-1088.
  • Ikuta, K. and Tani-ichi, S. (2009). Role of the IL-7 receptor in γδ T-cell development from hematopoietic stem cells. In "Hematopoietic Stem Cell Biology". Kondo, M., ed. Humana Press Inc. pp143-159.


  • Masui, N., Tani-ichi, S., Maki, K., and Ikuta, K. (2008). Transcriptional activation of mouse TCR Jγ4 germline promoter by Stat5. Mol. Immunol., 45:849-855.
  • Toda, T., Wada, H., Ogawa, S., Tani-ichi, S., and Ikuta, K. (2008). An efficient reporter assay for Stat5-dependent promoters. Anal. Biochem., 372:250-252.
  • Ogawa, S., Satake, M., and Ikuta, K. (2008). Physical and functional interactions between STAT5 and Runx transcriptional factors. J. Biochem., 143:695-709.
  • Maki, K. and Ikuta, K. (2008). MEK1/2 induces STAT5-mediated germline transcription of the TCRγ locus in response to IL-7R signaling. J. Immunol., 181:494-502.
  • Lee, H.-C., Headley, M. B., Iseki, M., Ikuta, K., and Ziegler, S. F. (2008). Inhibition of NF-κB-mediated TSLP expression by retinoid X receptor. J. Immunol., 181:5189-5193.
  • Hamada, S., Umemura, M., Shiono, T., Tanaka, K., Yahagi, A., Begum, M. D., Oshiro, K., Okamoto, Y., Watanabe, H., Kawakami, K., Roark, C., Born, W. K., O'Brien, R., Ikuta, K., Ishikawa, H., Nakae, S., Iwakura, Y., Ohta, T., and Matsuzaki, G. (2008). IL-17A produced by γδ T cells plays a critical role in innate immunity against Listeria monocytogenes infection in the liver. J. Immunol., 181:3456-3463.


  • Nakasone, C., Yamamoto, N., Nakamatsu, M., Kinjo, T., Miyagi, K., Uezu, K., Nakamura, K., Higa, F., Ishikawa, H., O'Brien, R. L., Ikuta, K., Kaku, M., Fujita, J., and Kawakami, K. (2007). Accumulation of gamma/delta T cells in the lungs and their roles in neutrophil-mediated host defense against pneumococcal infection. Microbes Infect., 9:251-258.
  • Shibata, H., Tani-ichi, S., Lee, H.-C., Maki, K., and Ikuta, K. (2007). Induction of the IL-7 receptor α chain in mouse peripheral B cells by glucocorticoids. Immunol. Lett., 111:45-50.


  • Simonian, P. L., Roark, C. L., del Valle, F. D., Palmer, B. E., Douglas, I. S., Ikuta, K., Born, W. K., O'Brien, R. L., and Fontenot, A. P. (2006). Regulatory role of γδ cells in the recruitment of CD4+ and CD8+ T cells to lung and subsequent pulmonary fibrosis. J. Immunol., 177:4436-4443.


  • Ye, S. K., Kim, T. J, Won, S. S., Yoon, T. J., Park, T. K., Yoo, Y. C., Kim, Y. N., Lee, H. C., Ikuta, K., Chung, M. H., Lee, K. H. (2005). Transcriptional regulation of the mouse interleukin-2 receptor β chain gene by Ets and Egr-1. Biochem. Biophys. Res. Commun., 329:1094-1101.
  • Lee, H.-C., Shibata, H., Ogawa, S., Maki, K., and Ikuta, K. (2005). Transcriptional regulation of the mouse IL-7 receptor α promoter by glucocorticoid receptor. J. Immunol., 174:7800-7806.


  • Gomez-del Arco, P., Maki, K., and Georgopoulos, K. (2004). Phosphorylation controls Ikaros's ability to negatively regulate the G1-S transition. Mol. Cell. Biol., 24: 2797-2807.


  • Watanabe, N., Ikuta, K., Okazaki, K., Nakase, H., Tabata, Y., Matsuura, M., Tamaki, H., Kawanami, C., Honjo, T., and Chiba, T. (2003). Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10 deficient mice. Dig. Dis. Sci., 48:408-418.
  • Kim-Saijo, M., Akamizu, T., Ikuta, K., Iida, Y., Ohmori, K., Matsubara, K., Matsuda, Y., Suzuki, M., Matsuda, F., and Nakao, K. (2003). Generation of a transgenic animal model of hyperthyroid Graves' disease. Eur. J. Immunol., 33:2531-2538.


  • Lee, H.-C., Tomiyama, K., Ye, S.-K., Kawai, K., and Ikuta, K. (2002). Seeding of dendritic epidermal T cells in the neonatal skin is reduced in 129 strain of mice. Immunol. Lett., 81:211-216.
  • Han, H., Tanigaki, K., Yamamoto, N., Kuroda, K., Yoshimoto, M., Nakahata, T., Ikuta, K., and Honjo, T. (2002). Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision. Int. Immunol., 14:637-645.
  • Watanabe, N., Ikuta, K., Nisitani, S., Chiba, T., and Honjo, T. (2002). Activation and differentiation of autoreactive B-1 cells by interleukin-10 induce autoimmune hemolytic anemia in Fas-deficient anti-erythrocyte immunoglobulin transgenic mice. J. Exp. Med., 196:141-146.
  • Lahn, M., Kanehiro, A., Takeda, K., Terry, J., Hahn, Y. S., Aydintug, M. K., Konowal, A., Ikuta, K., O'Brien, R. L., Gelfand, E. W., and Born, W. K. (2002). MHC class I-dependent Vγ4+ pulmonary T cells regulate αβ T cell-independent airway responsiveness. Proc. Natl. Acad. Sci. USA., 99:8850-8855.


  • Honda, K., Nakano H., Yoshida, H., Nishikawa, S., Rennert, P., Ikuta, K., Tamechika, M., Yamaguchi, K., Fukumoto, T., Chiba, T., and Nishikawa, S.-I. (2001). Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis. J. Exp. Med., 193:621-630.
  • Agata, Y., Katakai, T., Ye, S.-K., Sugai, M., Gonda, H., Honjo, T., Ikuta, K., and Shimizu, A. (2001). Histone acetylation determines the developmentally regulated accessibility for T cell receptor-γ gene recombination. J. Exp. Med., 193:873-879.
  • Ikuta. K., Lee, H.-C., and Ye, S.-K. (2001). Role of the IL-7 receptor in γδ T cell development. In "Gamma-delta T cells", Bergstresser, P. R., and Takashima, A., (eds). Chem. Immunol., 79:29-42.
  • Lee, H.-C., Ye, S.-K., Honjo, T., and Ikuta, K. (2001). Induction of germline transcription in the human T cell receptor γ locus by STAT5. J. Immunol., 167:320-326.
  • Ohba, Y., Ikuta, K., Ogura, A., Matsuda, J., Mochizuki, N., Nagashima, K., Kurokawa, K., Mayer, B. J., Maki, K., Miyazaki, J., and Matsuda, M. (2001). Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis. EMBO J., 20:3333-3341.
  • Ye, S.-K., Maki, K., Lee, H.-C., Ito, A., Kawai, K., Suzuki, H., Mak, T. W., Chien, Y., Honjo, T., and Ikuta, K. (2001). Differential roles of cytokine receptors in the development of epidermal γδ T cells. J. Immunol., 167:1929-1934.
  • Fagarasan, S., Kinoshita, K., Muramatsu, M., Ikuta, K., and Honjo, T. (2001). In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature, 413:639-643.
  • Ye, S.-K., Agata, Y., Lee, H.-C., Kurooka, H., Kitamura, T., Shimizu, A., Honjo, T., and Ikuta, K. (2001). The IL-7 receptor controls the accessibility of the TCRγ locus by Stat5 and histone acetylation. Immunity, 15:813-823.


  • Kina, T., Ikuta, K., Takayama, E., Wada, K., Majumdar, A. S., Weissman, I. L. and Katsura, Y. (2000). The monoclonal antibody TER-119 recognizes a molecule associated with glycophorin A and specifically marks the late stages of murine erythroid lineage. Brit. J. Heamatol., 109:280-287.
  • Fagarasan, S., Shinkura, R., Kamata, T., Nogaki, F., Ikuta, K., Tashiro, K., and Honjo, T. (2000). Alymphoplasia(aly)-type nuclear factor κB-inducing kinase (NIK) causes defects in secondary lymphoid tissue chemokine receptor signaling and homing of peritoneal cells to the gut-associated lymphatic tissue system. J. Exp. Med., 191:1477-1486.
  • Kamata, T., Nogaki, F., Fagarasan, S., Sakiyama, T., Kobayashi, I., Miyawaki, S., Ikuta, K., Muso, E., Yoshida, H., Sasayama, S., and Honjo, T. (2000). Increased frequency of surface IgA-positive plasma cells in the intestinal lamina propria and decreased IgA excretion in hyper IgA (HIGA) mice, a murine model of IgA nephropathy with hyperserum IgA. J. Immunol., 165:1387-1394.
  • Watanabe, N., Ikuta, K., Fagarasan, S., Yazumi, S., Chiba, T., and Honjo, T. (2000). Migration and differentiation of autoreactive B-1 cells induced by activated γδ T cells in anti-erythrocyte immunoglobulin transgenic mice. J. Exp. Med., 192:1577-1586.
  • Fagarasan, S., Shinkura, R., Kamata, T., Nogaki, F., Ikuta, K., and Honjo, T. (2000). Mechanism of B1 cell differentiation and migration in GALT. In "B1 lymphocytes in B cell neoplasia". Potter, M., and Melchers, F. eds. Cur. Top. Microbiol. Immunol., vol. 252. pp221-229.
  • O'Brien, R. L., Yin, X., Huber, S. A., Ikuta, K., and Born, W. K. (2000). Depletion of a γδ T cell subset can increase host resistance to a bacterial infection. J. Immunol., 165:6472-6479.