胸腺におけるネオ・セルフ生成機構

• Project Area: Creation, function and structure of neo-self
• Project/Area Number: 16H06496
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokushima
• Principal Investigator: 松本 満 徳島大学, 先端酵素学研究所, 教授 (60221595)
• Co-Investigator(Kenkyū-buntansha): 吉開 泰信 九州大学, 生体防御医学研究所, 学術研究員 (90158402)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Project Status: Granted (Fiscal Year 2020)
• Budget Amount: ¥201,110,000 (Direct Cost: ¥154,700,000、Indirect Cost: ¥46,410,000); Fiscal Year 2020: ¥38,870,000 (Direct Cost: ¥29,900,000、Indirect Cost: ¥8,970,000); Fiscal Year 2019: ¥38,870,000 (Direct Cost: ¥29,900,000、Indirect Cost: ¥8,970,000); Fiscal Year 2018: ¥38,870,000 (Direct Cost: ¥29,900,000、Indirect Cost: ¥8,970,000); Fiscal Year 2017: ¥38,870,000 (Direct Cost: ¥29,900,000、Indirect Cost: ¥8,970,000); Fiscal Year 2016: ¥45,630,000 (Direct Cost: ¥35,100,000、Indirect Cost: ¥10,530,000)
• Keywords: 胸腺 / ネオ・セルフ / 自然T細胞 / 抗原提示細胞 / 免疫学的自己 / Aire / Vγ6+γδTh17細胞 / innate T cell / 胸腺上皮細胞 / 抗原認識機構 / 自己抗原 / 自己免疫疾患 / 自己寛容 / 自然免疫T細胞

Outline of Annual Research Achievements

Aire欠損症は単一遺伝子の異常による自己免疫病態を示すため、胸腺における免疫学的自己の定義付けに最適な研究対象である。今年度はAireの標的遺伝子を同定するための遺伝子改変マウスを樹立した。すなわち、P2Aリンカーを用いて内在性のAire遺伝子座にマウスAire cDNAを２コピー付加したノックインマウスを作製した（以下、3xAire-KIと略す）。実際に、Real-time PCR法によって胸腺髄質上皮細胞（mTEC）からのmouse Aireの発現レベルを測定し、ヘテロ3xAire-KIでは野生型の２倍、ホモ3xAire-KIにおいては野生型の３倍と期待通りのAire mRNAの発現を認めた。そこで、Aireの過剰発現による胸腺髄質上皮細胞（mTEC）のTranscriptome解析を実施したところ、意外にもAire欠損マウスと同様に様々な遺伝子発現の低下を認めた。今後は、そのメカニズムを解析する予定である。他方、胸腺で分化する過程でインターロイキン（IL）-17A産生能を有するVγ6+γδTh17細胞は、様々な感染症や自己免疫疾患でT細胞レセプター（TCR）依存性に活性化されることから、胸腺内と末梢の炎症の場で発現する「ネオ・セルフ」抗原を認識していると考えられる。今回、Vγ6特異的モノクローナル抗体(1C10-1F7 mAb)を用いて, Vγ6+γδTh17細胞の胸腺での分化と末梢での維持に関わる分子と感染症、自己免疫病での役割を調べた。その結果、1）MHCクラスII分子欠損の胸腺ではVγ6+γδTh17細胞は増加する。２）SLAM-SAPのシグナルは末梢でのVγ6+γδTh17細胞を減少させる。3)Vγ6+γδTh17細胞は大腸菌の感染早期の防御に働く。5）imiquimod投与乾癬モデルで1C10-1F7 mAbがその治療に効果があることを明らかにした。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

当初の計画通り、P2Aリンカーを用いて胸腺髄質上皮細胞（mTEC）においてAire蛋白を過剰に発現するノックインマウスの作出に成功した。それによってこれまでに我々が主張して来たAireのmTEC分化誘導作用ならびにそれによる自己抗原の発現調節機構を明らかにする予定である。この方法論を用いることによって、AireがmTEC特異的に発現することの生理的意義やAireの過剰発現による病理学的変化の検証といった多くの課題に取り組むことが出来ることになる。一方、Vγ6+γδTh17細胞は胸腺内と末梢の炎症の場で発現する「ネオ・セルフ」抗原を認識していると考えられるが、その性状を明らかにするために必要となる新規モノクローナル抗体の樹立にも成功しており、本年度の研究計画はおおむね順調に進展していると言える。ただ、当初、Aireに関する研究成果を報告する予定であったThe 3rd International Congress on Rare DiseasesがCOVID-19の蔓延により延期となった点は残念であった。

Strategy for Future Research Activity

我々はAire胸腺髄質上皮細胞の分化を誘導するメカニズムによって自己寛容の成立を制御するモデルを提唱し、その妥当性を検証してきている。そのため、この度のAireがmTECの分化誘導を通じて自己抗原の発現を調節しているとする知見は、きわめて重要であり、今後は同様なメカニズムがAire欠損状態においても自己抗原発現低下の原因となっているか否かをAire欠損マウスを用いたTranscriptome解析やSingle-cell analysisによって確認する必要がある。なお、COVID-19の蔓延により延期となったThe 3rd International Congress on Rare Diseasesについては、開催された際にはTissue-specific autoimmunity controlled by Aire, a gene responsible for APECEDのタイトルで報告する予定である。一方、Vγ6+γδTh17細胞が認識する胸腺内と末梢の炎症の場で発現する「ネオ・セルフ」抗原の性状を明らかにする研究を引き続き行う計画である。

Research Products

• [Int'l Joint Research] China Medical University(中国)
• [Int'l Joint Research] Universidade do Porto(ポルトガル)
• [Int'l Joint Research] ワシントン大学(米国)
• [Int'l Joint Research] ミュンヘン大学(ドイツ)
• [Journal Article] Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms (2020)
  • Author(s): Matsumoto Minoru、Tsuneyama Koichi、Morimoto Junko、Hosomichi Kazuyoshi、Matsumoto Mitsuru、Nishijima Hitoshi
  • Journal Title: International Immunology Volume: 32 Pages: 117-131
  • DOI: 10.1093/intimm/dxz066
  • Peer Reviewed / Open Access
• [Journal Article] Impaired upregulation of Stat2 gene restrictive to pancreatic β-cells is responsible for virus-induced diabetes in DBA/2 mice. (2020)
  • Author(s): Mine, K.; Nagafuchi, S.; Hatano, S.; Tanaka, K.; Mori, H.; Takahashi, H.; Anzai, K.; Yoshikai, Y.
  • Journal Title: Biochem Biophys Res Commun 521:853-860 Volume: 521 Pages: 853-860
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• [Journal Article] IL-7R-Dependent Phosphatidylinositol 3-Kinase Competes with the STAT5 Signal to Modulate T Cell Development and Homeostasis. (2020)
  • Author(s): Cui G, Shimba A, Ma G, Takahara K, Tani-Ichi S, Zhu Y, Asahi T, Abe A, Miyachi H, Kitano S, Hara T, Yasunaga JI, Suwanai H, Yamada H, Matsuoka M, Ueki K, Yoshikai Y, Ikuta K.
  • Journal Title: J Immunol. Volume: 204 Pages: 844-857
  • DOI: 10.4049/jimmunol.1900456
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• [Journal Article] Effects of an 8-Week Protein Supplementation Regimen with Hyperimmunized Cow Milk on Exercise-Induced Organ Damage and Inflammation in Male Runners: A Randomized, Placebo Controlled, Cross-Over Study (2020)
  • Author(s): Ma S, Tominaga T, Kanda K, Sugama K, Omae C, Hashimoto S, Aoyama K, Yoshikai Y, Suzuki K.
  • Journal Title: Biomedicines Volume: 8
  • DOI: 10.3390/biomedicines8030051
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• [Journal Article] Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial (2019)
  • Author(s): Tanaka Y, Hirose Y, Yamamoto Y, Yoshikai Y, Murosaki S.
  • Journal Title: Eur. J. Nutr. Volume: 59 Pages: 2641-2649
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  • Peer Reviewed
• [Journal Article] S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches (2019)
  • Author(s): Kunimura K, Sakata D, Tun X, Uruno T, Ushijima M, Katakai T, Shiraishi A, Aihara R, Kamikaseda Y, Matsubara K, Kanegane H, Sawa S, Eberl G, Ohga S, Yoshikai Y, Fukui Y.
  • Journal Title: Cell Rep Volume: 29 Pages: 2823-2834
  • DOI: 10.1016/j.celrep.2019.10.091
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term use of interferon-β in multiple sclerosis increases Vδ1(-)Vδ2(-)Vγ9(-) γδ T cells that are associated with a better outcome (2019)
  • Author(s): Maimaitijiang G, Watanabe M, Shinoda K, Isobe N, Nakamura Y, Masaki K, Matsushita T, Yoshikai Y, Kira J.
  • Journal Title: J. Neuroinflammation Volume: 16 Pages: 179-179
  • DOI: 10.1186/s12974-019-1574-5
  • Peer Reviewed / Open Access
• [Journal Article] Lactobacillus plantarum L-137 upregulates hyaluronic acid production in epidermal cells and fibroblasts in mice (2019)
  • Author(s): Nakai H, Hirose Y, Murosaki S, Yoshikai Y.
  • Journal Title: Microbiol Immunol. Volume: 63 Pages: 367-378
  • DOI: 10.1111/1348-0421.12725
  • Peer Reviewed
• [Journal Article] Development of a new monoclonal antibody specific to mouse Vg6 chain (2019)
  • Author(s): Hatano S, Tun X, Noguchi N, Yue D, Yamada H, Sun X, Matsumoto M, Yoshikai Y.
  • Journal Title: Life Sci Alliance Volume: 2 Pages: 1-12
  • DOI: 10.26508/lsa.201900363
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD30L/CD30 signal transduction protects against psoriasiform skin inflammation by suppressing Th17-related cytokine production by Vγ4+ γδT cells T cells (2019)
  • Author(s): Yue D, You Y, Zhang X, Wang B, Wang X, QiR, Yang F, Meng X, Yoshikai Y, Wang Y and , Sun X.
  • Journal Title: J Autoimmun. Volume: 101 Pages: 70-85
  • DOI: 10.1016/j.jaut.2019.04.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD30 ligand deficiency accelerates glioma progression by promoting the formation of tumor immune microenvironment (2019)
  • Author(s): Duan J, Gao Y, Zhang X, Wang X, Wang B, Meng X, Yoshikai Y, Wang Y, and Sun X.
  • Journal Title: Int Immunopharmacol. Volume: 71 Pages: 350-360
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• [Journal Article] Viruses with masked pathogenicity and genetically susceptible hosts-How to discover potentially pathogenic viruses (2019)
  • Author(s): Nagafuchi Seiho、Mine Keiichiro、Takahashi Hirokazu、Anzai Keizo、Yoshikai Yasunobu
  • Journal Title: J Med Virol. Volume: 91 Pages: 1365-1367
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  • Peer Reviewed / Open Access
• [Journal Article] ヒトAIREを発現させたNODマウスに認められる自己免疫応答 (2019)
  • Author(s): 西嶋 仁、松本 満
  • Journal Title: 臨床免疫・アレルギー科 Volume: 71 Pages: 490-496
• [Journal Article] AIRE - The Autoimmune Regulator (2019)
  • Author(s): Matsumoto Minoru、Nishijima Hitoshi、Morimoto Junko、Tsuneyama Koichi、Matsumoto Mitsuru
  • Journal Title: eLS Volume: 1 Pages: 1-8
  • DOI: 10.1002/9780470015902.a0027281
  • Peer Reviewed
• [Journal Article] Fas/FasL signaling is critical for the survival of exhausted antigen-specific CD8+ T cells during tumor immune response. (2019)
  • Author(s): Yajima T, Hoshino K, Muranushi R, Mogi A, Onozato R, Yamaki E, Kosaka T, Tanaka S, Shirabe K, Yoshikai Y and Kuwano H.
  • Journal Title: Molecular Immunology Volume: 107 Pages: 97-105
  • DOI: 10.1016/j.molimm.2019.01.014
  • Peer Reviewed
• [Journal Article] CD30L/CD30 signal transduction protects against psoriasiform skin inflammation by suppressing Th17-related cytokine production by Vγ4+ γδT cells T cells． (2019)
  • Author(s): Yue D, You Y, Zhang X, Wang B, Wang X, QiR, Yang F, Meng X, Yoshikai Y, Wang Y and , Sun X.
  • Journal Title: J.Autoimmunity Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of a new monoclonal antibody specific to the murine Vγ6 chain. (2019)
  • Author(s): Hatano S, Tun X, Noguchi N, Yue D, Yamada H, Sun X, Matsumoto M, and Yoshikai Y.
  • Journal Title: Life Science Alliance Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE) (2018)
  • Author(s): Nishijima Hitoshi、Kajimoto Tatsuya、Matsuoka Yoshiki、Mouri Yasuhiro、Morimoto Junko、Matsumoto Minoru、Kawano Hiroshi、Nishioka Yasuhiko、Uehara Hisanori、Izumi Keisuke、Tsuneyama Koichi、Okazaki Il-mi、Okazaki Taku、Hosomichi Kazuyoshi、Shiraki Ayako、Shibutani Makoto、Mitsumori Kunitoshi、Matsumoto Mitsuru
  • Journal Title: J. Autoimmunity Volume: 86 Pages: 75-92
  • DOI: 10.1016/j.jaut.2017.09.006
  • NAID: 120006532435
  • Peer Reviewed / Open Access
• [Journal Article] Aire Controls in Trans the Production of Medullary Thymic Epithelial Cells Expressing Ly-6C/Ly-6G (2018)
  • Author(s): Morimoto Junko、Nishikawa Yumiko、Kakimoto Takumi、Furutani Kohei、Kihara Naoki、Matsumoto Minoru、Tsuneyama Koichi、Kozono Yuko、Kozono Haruo、Hozumi Katsuto、Hosomichi Kazuyoshi、Nishijima Hitoshi、Matsumoto Mitsuru
  • Journal Title: Journal of immunology Volume: 201 Pages: 3244-3257
  • DOI: 10.4049/jimmunol.1800950
  • Peer Reviewed / Open Access
• [Journal Article] Association of Decreased Percentage of Vδ2+Vγ9+ γδ T Cells With Disease Severity in Multiple Sclerosis (2018)
  • Author(s): Maimaitijiang G, Shinoda K, Nakamura Y, Masaki K, Matsushita T, Isobe N, Yamasaki R, Yoshikai Y, Kira J.
  • Journal Title: Front Immunol. Volume: 9 Pages: 1-10
  • DOI: 10.3389/fimmu.2018.00748
  • Peer Reviewed / Open Access
• [Journal Article] The presence of IgG ACPA-IgM RF immune complex detected as IgM ACPA in the serum of rheumatoid arthritis patients. (2018)
  • Author(s): Haraguchi A, Yamada H, Kondo M, Okazaki K, Fukushi J, Oyamada A, Yoshikai Y and Nakashima Y.
  • Journal Title: Clin Exp Rheumatol Volume: 36 Pages: 612-618
  • Peer Reviewed
• [Journal Article] IL-21 induces short-lived effector CD8+ T cells but does not inhibit their exhaustion after Mycobacterium bovis Bacillus Calmette-Guerin infection in mice. (2018)
  • Author(s): Noguchi N, Nakamura R, Hatano S, Yamada H, Sun X, Ohara N, and Yoshikai Y.
  • Journal Title: Infect Immun Volume: 86
  • DOI: 10.1128/iai.00147-18
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cutting Edge: B cells expressing cyclic citrullinated peptide-specific antigen receptor are tolerized in normal conditions. (2018)
  • Author(s): Yamada H, Ozawa T, Kishi H, Okada S, Nakashima Y, Muraguchi A and Yoshikai Y.
  • Journal Title: The Journal of Immunology Volume: 201 Pages: 3492-3496
  • DOI: 10.4049/jimmunol.1800826
  • Peer Reviewed
• [Journal Article] Glucocorticoids drive diurnal oscillations in T cell distribution and responses by inducing interleukin-7 receptor and CXCR4. (2018)
  • Author(s): Shimba A, Cui G, Tani-ichi S, Ogawa M, Abe S, Okazaki F, Kitano S, Miyach H, Yamada H, Hara T, Yoshikai Y, Nagasawa T, Schutz G, Ikuta K.
  • Journal Title: Immunity Volume: 48 Pages: 286-298
  • DOI: 10.1016/j.immuni.2018.01.004
  • NAID: 120006401712
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mode of Tolerance Induction and Requirement for Aire Are Governed by the Cell Types That Express Self-Antigen and Those That Present Antigen. (2017)
  • Author(s): Mouri Y, Ueda Y, Yamano T, Matsumoto M, Tsuneyama K, Kinashi T, and Matsumoto M.
  • Journal Title: J Immunol. Volume: 199 Pages: 3959-3971
  • DOI: 10.4049/jimmunol.1700892
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD5－NK1.1+γδT cells that develop in a Bcl11b-independent manner participate in early protection against infection. (2017)
  • Author(s): Hatano S, Murakami T, Noguchi N, Yamada H, Yoshikai Y.
  • Journal Title: Cell Reports Volume: 21 Pages: 1191-1202
  • DOI: 10.1016/j.celrep.2017.10.007
  • Peer Reviewed / Open Access
• [Journal Article] In vivo blockade of T cell development reveals alternative pathways for generation of intraepithelial lymphocytes in mice (2017)
  • Author(s): Mondoon Surenchimeg、Shibata Kensuke、Yoshikai Yasunobu
  • Journal Title: Immunology Letters Volume: 191 Pages: 40-46
  • DOI: 10.1016/j.imlet.2017.09.008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Subtyping of Type 1 Diabetes as Classified by Anti-1 GAD Antibody, IgE levels, and Tyrosine kinase 2 (TYK2) Promoter Variant in the Japanese. (2017)
  • Author(s): Mine K, Hirakawa K, Kondo S, Minami M, Okada A, Tsutsu N, Yokogawa Y, Hibio Y, Kojima F, Fujimoto S, Kurisaki H, Katsuta H,2 Anzai K, Yoshikai Y, Nagafuchi S and the West Japan Pathogenesis of Diabetes Study Group
  • Journal Title: EBioMedicine Volume: 23 Pages: 46-51
  • DOI: 10.1016/j.ebiom.2017.08.012
  • Peer Reviewed / Open Access
• [Journal Article] Th1 is the predominant helper T cell subset that produces GM-CSF in the joint of rheumatoid arthritis. (2017)
  • Author(s): Yamada H, Haraguchi A, Sakuraba K, Okazaki K, Fukushi JI, Mizu-Uchi H, Akasaki Y, Esaki Y, Kamura S, Fujimura K, Kondo M, Miyahara H, Nakashima Y, Yoshikai Y.
  • Journal Title: RMD Open Volume: 3
  • DOI: 10.1136/rmdopen-2017-000487
  • Peer Reviewed / Open Access
• [Journal Article] Identification of embryonic precursor cells that differentiate into thymic epithelial cells expressing autoimmune regulator. (2016)
  • Author(s): Akiyama N, Takizawa N, Miyauchi M, Yanai H, Tateishi R, Shinzawa M, Yoshinaga R, Kurihara M, Demizu Y, Yasuda H, Yagi S, Wu G, Matsumoto M, Sakamoto R, Yoshida N, Penninger JM, Kobayashi Y, Inoue J, Akiyama T.
  • Journal Title: J Exp Med Volume: 213 Pages: 1441-1458
  • DOI: 10.1084/jem.20151780
  • NAID: 120006532434
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol Mannosides to Promote a Th1 Response during Infection (2016)
  • Author(s): Toyonaga K, Torigoe S, Motomura Y, Kamichi T, Hayashi JM, Morita YS, Noguchi N, Chuma Y, Kiyohara H, Matsuo K, Tanaka H, Nakagawa Y, Sakuma T, Ohmuraya M, Yamamoto T, Umemura M, Matsuzaki G, Yoshikai Y, Yano I, Miyamoto T, Yamasaki S.
  • Journal Title: Immunity. Volume: 45 Pages: 1245-1257
  • DOI: 10.1016/j.immuni.2016.10.012
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Two types of IL-17A-producing γδ T cells in protection against pulmonary infection with Klebsiella pneumoniae (2016)
  • Author(s): Murakami T., Hatano S., Yamada H., Iwakura Y., Yoshikai Y.
  • Journal Title: J Infect Dis. Volume: 214 Pages: 1752-1761
  • DOI: 10.1093/infdis/jiw443
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IL-21 inhibits IL-17A-producing γδ T cell response after infection with Bacillus Calmette-Guerin via induction of apoptosis (2016)
  • Author(s): Huang Y., Matsumura Y., Hatano, S., Noguchi N., Murakamia, T., Iwakura Y., Sun X., Oharad N., Yoshikai Y.
  • Journal Title: Innate Immun. Volume: 22 Pages: 588-597
  • DOI: 10.1177/1753425916664125
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] IL-21/IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice (2016)
  • Author(s): Wang, Y. Jiang, X., Zhu, J., Yue, D., Zhang, X., Wang, X., You, Y., Wang, B., Xu, Y., Lu, C, Sun, X., Yoshikai Y.
  • Journal Title: Sci Rep. Volume: 22 Pages: 31881-31881
  • DOI: 10.1038/srep31881
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Interleukin-21-signaling in B cells, but not in T cells, is indispensable for the development of collagen-induced arthritis in mice (2016)
  • Author(s): Sakuraba K., Oyamada A., Fujimura K., Spolski R., Iwamoto Y., Leonard I.W., Yoshikai Y., Yamada H.
  • Journal Title: Arthritis Research & Therapy Volume: 17 Pages: 188-188
  • DOI: 10.1186/s13075-016-1086-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Equol inhibits prostate cancer growth via degradation of the androgen receptor by Skp2. (2016)
  • Author(s): Itsumi M, Shiota M, Takeuchi A, Kashiwagi E, Inokuchi J, Tatsugami K, Kajioka S, Uchiumi T, Naito S, Eto M, Yokomizo A.
  • Journal Title: Int Immunopharmacol. Volume: in press Pages: 327-331
  • DOI: 10.1016/j.intimp.2016.03.007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Aire-dependent establishment of self-tolerance studied by genetically modified mice (2019)
  • Author(s): Mitsuru Matsumoto, Junko Morimoto, Minoru Matsumoto, Koichi Tsuneyama, Ryuichiro Miyazawa, Hitoshi Nishijima
  • Organizer: EMBO Workshop ThymE
  • Int'l Joint Research / Invited
• [Presentation] Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms (2019)
  • Author(s): Minoru Matsumoto, Mitsuru Matsumoto
  • Organizer: The 18th Awaji International Forum on Infection and Immunity
  • Int'l Joint Research
• [Presentation] The analysis of roles of Vγ6 γδ T cells in host defense using a new monoclonal antibody specific to mouse Vγ6 chain (2019)
  • Author(s): Shinya Hatano, Xin Tun, Dan Yue, Naoto Noguchi, Xun Sun, Mitsuru Matsumoto, Yasunobu Yoshikai.
  • Organizer: The 18th Awaji International Forum on Infection and Immunity
  • Int'l Joint Research
• [Presentation] Aire-dependent establishment of self-tolerance (2019)
  • Author(s): Matsumoto M, Morimoto J, Matsumoto M, Tsuneyama K, Miyazawa R, Nishijima H
  • Organizer: The 17th International Congress of Immunology
  • Int'l Joint Research
• [Presentation] 胸腺におけるネオ・セルフ生成機構 (2019)
  • Author(s): 松本 満
  • Organizer: 第92回日本生化学会大会
• [Presentation] 新規抗マウスVγ6抗体を用いたIL-17A産生Vγ6γδ型T細胞の生体防御機構における役割の解明 (2019)
  • Author(s): Tun Xin、畑野晋也、Dan Yue、野口直人、岩倉洋一郎、Xun Sun、吉開泰信
  • Organizer: 第31回日本比較免疫学会学術集会－第30回日本生体防御学会学術総会の合同集会
• [Presentation] Dermal Vγ6 T17 cells are responsible for Psoriasis-like dermatitis in mice (2019)
  • Author(s): Xin Tun, Dan Yue,Shinya Hatano, Yoichiro Iwakura, Xun Sun, Yasunobu Yoshikai.
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] Development of IL-17A+ Vγ6 γδ T cells in mouse thymus (2019)
  • Author(s): Shinya Hatano, Xin Tun, Mitsuru Matsumoto, Yoshihiro Baba, Yasunobu Yoshikai.
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] 胸腺髄質上皮細胞に発現する転写調節因子Aireを用いた自己免疫病態の解析 (2019)
  • Author(s): 松本 満
  • Organizer: 第29回日本内分泌学会臨床内分泌代謝Update
  • Invited
• [Presentation] Aireを高発現する胸腺髄質上皮細胞の免疫学的機能とトランスクリプトーム解析 (2019)
  • Author(s): 西嶋 仁、杉田瑞季、森本純子、松本 穣、松本 満
  • Organizer: 第42回日本分子生物学会
• [Presentation] Antigen transfer from thymic epithelial cells to DCs contributes to the production of thymic Tregs (2019)
  • Author(s): Junko Morimoto, Hitoshi Nishijima, Minoru Matsumoto, Mitsuru Matsumoto
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] Characterization of Aire-expressing DCs with a high-sensitivity and high-fidelity Aire-reporter strain Minoru Matsumoto, Hitoshi Nishijima, Ryuichiro Miyazawa, Junko Morimoto, Koichi Tsuneyama, Mitsuru Matsumoto (2019)
  • Author(s): Minoru Matsumoto, Hitoshi Nishijima, Ryuichiro Miyazawa, Junko Morimoto, Koichi Tsuneyama, Mitsuru Matsumoto
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] 新規抗マウスVγ6抗体を用いたVγ6リガンドの探索 (2019)
  • Author(s): 畑野晋也, 吉開泰信
  • Organizer: 新学術領域研究ネオ・セルフの生成・機能・構造 第2回若手の会 (第4回 領域班会議)
• [Presentation] 抗CCP抗体遺伝子導入マウスのB細胞分化機能解析 (2019)
  • Author(s): 山田久方、小澤龍彦、岸裕幸、岡田誠司、中島康晴、村口篤、吉開泰信
  • Organizer: 第57回九州リウマチ学会
• [Presentation] Expression of Ly6C/6G defines a novel subset of medullary thymic epithelial cells (2018)
  • Author(s): Junko Morimoto, Yumiko Nishikawa, Naoki Kihara, Kazuyoshi Hosomichi, Hitoshi Nishijima, Mitsuru Matsumoto
  • Organizer: Immunology 2018 - AAI Annual Meeting
  • Int'l Joint Research
• [Presentation] Manipulation of thymic and peripheral tolerance by AIRE defines distinct tissue-specific autoimmunity (2018)
  • Author(s): Minoru Matsumoto, Hitoshi Nishijima, Junko Morimoto, Koichi Tsuneyama and Mitsuru Matsumoto
  • Organizer: 11th International Congress on Autoimmunity
  • Int'l Joint Research
• [Presentation] Amelioration of diabetes development in NOD by the transgenic human AIRE expression in DCs (2018)
  • Author(s): Mitsuru Matsumoto
  • Organizer: 第47回 日本免疫学会学術集会
  • Invited
• [Presentation] 「TYK2多型、IgE、抗GAD抗体から考えられた日本人T1D患者の特徴」 (2018)
  • Author(s): 三根敬一朗、平川可奈、日比生由美、小島夫美子、栗崎宏憲、藤本秀士、南昌江、岡田朗、筒信隆、近藤しおり、横川泰、吉開泰信、森仁恵、松田やよい、高橋宏和、安西慶三、永淵正法
  • Organizer: 第61回 日本糖尿病学会年次学術集会
• [Presentation] Host defense by γδ T cells recapitulates their thymic ontogeny. (2018)
  • Author(s): Shinya Hatano and Yasunobu Yoshikai.
  • Organizer: The 1st International Symposium on NEO-SELF.
• [Presentation] マウスVδ6陽性細胞の特性 －新規抗体を用いて－ (2018)
  • Author(s): 畑野晋也, 吉開泰信
  • Organizer: 新学術領域「ネオ・セルフ」第3回領域全体班会議
• [Presentation] EMC-D virus-induced diabetes in DBA/2 mice (2018)
  • Author(s): K. Mine , S. Nagafuchi , H. Takahashi , Y. Yoshikai , H. Mori , Y. Matsuta , K.Anzai
  • Organizer: 欧州糖尿病学会（European Association for the Study of Diabetes：EASD)第54回年次集会
• [Presentation] 「DBA/2マウスにおけるウイルス性1型糖尿病感受性遺伝子の探索」 (2018)
  • Author(s): 三根敬一朗、森 仁恵、田中賢一、畑野晋也、高橋 宏和、吉開泰信、安西慶三、永淵正法
  • Organizer: 第56回 日本糖尿病学会 九州地方会
• [Presentation] Characteristics of Vγ6+ γδ T cells in mice using novel antibody specific for Vγ6 chain. (2018)
  • Author(s): Shinya Hatano, Naoto Noguchi, Hisakata Yamada, Yasunobu Yoshikai.
  • Organizer: 第47回日本免疫学会学術集会
• [Presentation] Aire-dependent subset of mTECs with tolerogenic functions is defined by Ly6 family protein expression. (2018)
  • Author(s): Mitsuru Matsumoto, Junko Morimoto, Minoru Matsumoto, Koichi Tsuneyama, Hitoshi Nishijima
  • Organizer: ThymOz8
  • Int'l Joint Research
• [Presentation] Acquisition of the resistance to autoimmune diabetes by the expression of human AIRE in BM-derived APCs in NOD (2018)
  • Author(s): Minoru Matsumoto, Hitoshi Nishijima, Junko Morimoto, Koichi Tsuneyama, Mitsuru Matsumoto
  • Organizer: ThymOz8
  • Int'l Joint Research
• [Presentation] Bcl11b-independent CD5－NK1.1+γδ T cells participate in early protection against Listeria infection (2018)
  • Author(s): 畑野晋也，村上哲晋，野口直人，山田久方，吉開泰信
  • Organizer: 第91回細菌学会総会
• [Presentation] IL-21 induces short-lived effector CD8+ T cells after BCG infection in mice. (2018)
  • Author(s): 野口直人，中村梨沙，畑野晋也，山田久方，Xun Sun，大原直也，吉開泰信
  • Organizer: 第91回細菌学会総会
• [Presentation] Expression of Ly6C/6G defines a novel Aire-dependent subset of medullary thymic epithelial cells with tolerogenic function (2017)
  • Author(s): Morimoto, J., Nishikawa, Y., Nishijima, H., Matsumoto, M.
  • Organizer: 12th International Congress on SLE
  • Place of Presentation: Melbourne (Australia)
  • Year and Date: 2017-03-27
  • Int'l Joint Research
• [Presentation] γδ型 T細胞-原始的T細胞として- (2017)
  • Author(s): 吉開泰信
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2017-03-20
  • Invited
• [Presentation] Paradoxical development of polymyositis-like autoimmunity through augmented expression of AIRE (2017)
  • Author(s): Nishijima, H., Mouri, Y., Morimoto, J., Matsumoto, M.
  • Organizer: 7th International Workshop of Kyoto T Cell Conference
  • Place of Presentation: 芝蘭会館(京都府・京都市)
  • Year and Date: 2017-03-17
  • Int'l Joint Research
• [Presentation] Paradoxical development of polymyositis-like autoimmunity through augmented expression of human AIRE in mice (2017)
  • Author(s): Nishijima, H., Mouri, Y., Morimoto, J., Matsumoto, M.
  • Organizer: Controversies in Rheumatology and Autoimmunity 2017
  • Place of Presentation: Bologna (Italy)
  • Year and Date: 2017-03-09
• [Presentation] Expression of Ly6C/6G defines a novel subset of medullary thymic epithelial cells. (2017)
  • Author(s): Junko Morimoto, Yumiko Nishikawa, Naoki Kihara, Kazuyoshi Hosomichi, Hitoshi Nishijima, Mitsuru Matsumoto
  • Organizer: 5th Annual Meeting of the International Cytokine and Interferon Society
  • Int'l Joint Research
• [Presentation] Tissue-specific autoimmune response controlled by Aire. (2017)
  • Author(s): Mitsuru Matsumoto
  • Organizer: 第46回日本免疫学会総会
  • Invited
• [Presentation] Development of new monoclonal antibody specific for murine Vγ6 chain. (2017)
  • Author(s): Shinya Hatano, Hisakata Yamada, Yasunobu Yoshikai.
  • Organizer: 第46回日本免疫学会総会
• [Presentation] IL-21 induces short-lived effector CD8+ T cells but does not inhibit their exhaustion after Mycobacterium bovis Bacillus Calmette-Guerin infection in mice. (2017)
  • Author(s): Naoto Noguchi, Risa Nakamura, Shinya Hatano, Hisakata Yamada, Xun Sun, Naoya Ohara, Yasunobu Yoshikai.
  • Organizer: 第46回日本免疫学会総会
• [Presentation] 関節リウマチにおけるGM-CSF産生CD4T細胞サブセットの同定 (2017)
  • Author(s): 山田久方，原口明久，櫻庭康司，岡崎賢，福士純一，水内秀城，赤崎幸穂，江崎幸雄，嘉村聡志，藤村謙次郎，近藤正一，宮原寿明，中島康晴，吉開泰信
  • Organizer: 第45回日本臨床免疫学会総会
• [Presentation] Recognition of mycobacterial lipid by Dendritic cell immunoactivating receptor (2016)
  • Author(s): Kenji Toyonaga, Shota Torigoe, Yoshitomo Motomura, Takane Kamichi, Kazuhiro Matuo, Yasunobu Yoshikai, Sho Yamasaki.
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県・宜野湾市)
  • Year and Date: 2016-12-07
• [Presentation] A critical role of primitive γδ T cells developing (from DN2a stage) independently of Bcl11b in early host defense (2016)
  • Author(s): Shinya Hatano, Tesshin Murakami, Yumiko Matsumura, Hisakata Yamada, Yasunobu Yoshikai
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県・宜野湾市)
  • Year and Date: 2016-12-05
• [Presentation] Possible defect in the Treg production in mice overexpressing AIRE/Aire which exhibit muscle-specific autoimmunity (2016)
  • Author(s): Yuji Fukushima, Hisakata Yamada, Yasunobu Yoshikai, Nagahiro Minato, Masakazu Hattori
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県・宜野湾市)
  • Year and Date: 2016-12-05
• [Presentation] CD153-CD30 interaction is involved in immunosenescence of T cells and spontaneous germinal center reactions. (2016)
  • Author(s): Yuji Fukushima, Hisakata Yamada, Yasunobu Yoshikai, Nagahiro Minato, Masakazu Hattori
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県・宜野湾市)
  • Year and Date: 2016-12-05
• [Presentation] In vivo blockade of T cell development defines developmental pathways of intraepithelial lymphocytes in mice (2016)
  • Author(s): Surenchimeg Mondoon, Kensuke Shibata, Yasunobu Yoshikai
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県・宜野湾市)
  • Year and Date: 2016-12-05
• [Presentation] Immunological tolerance mediated by Aire (2016)
  • Author(s): Matsumoto, M.
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県・横浜市)
  • Year and Date: 2016-12-01
  • Invited
• [Presentation] Massive infiltration of macrophages and eosinophils in the muscle of mice overexpressing Aire in thymic and peripheral antigen-presenting cells (2016)
  • Author(s): Nishijima, H., Matsumoto, M.
  • Organizer: Cell Symposia
  • Place of Presentation: Sicily (Italy)
  • Year and Date: 2016-09-20
  • Int'l Joint Research
• [Presentation] 異なる活性化経路をもつ2種類のIL-17A産生γδT細胞が、肺炎桿菌に対する感染防御に重要な役割を果たす (2016)
  • Author(s): 村上哲晋、畑野晋也、山田久方、岩倉洋一郎、吉開泰信
  • Organizer: 第27回日本生体防御学会学術総会
  • Place of Presentation: 九州大学（福岡県・福岡市）
  • Year and Date: 2016-07-09
• [Presentation] Bcl11b非依存性primitive γδT cellによる感染防御機構 (2016)
  • Author(s): 畑野晋也、村上哲晋、野口直人、松村友美子、山田久方、吉開泰信
  • Organizer: 第27回日本生体防御学会学術総会
  • Place of Presentation: 九州大学（福岡県・福岡市）
  • Year and Date: 2016-07-09
• [Presentation] γδ型 T細胞と生体防御 (2016)
  • Author(s): 吉開泰信
  • Organizer: 第27回日本生体防御学会学術総会
  • Place of Presentation: 九州大学（福岡県・福岡市）
  • Year and Date: 2016-07-08
  • Invited
• [Book] Thymus Transcriptome and Cell Biology (2019)
  • Author(s): Minoru Matsumoto, Pedro M. Rodrigues, Laura Sousa, Koichi Tsuneyama, Mitsuru Matsumoto, Nuno L. Alves
  • Total Pages: 31
  • Publisher: Springer International Publishing
  • ISBN: 9783030120405
• [Book] JANEWAY’S免疫生物学 (監訳 笹月健彦、吉開泰信) (2019)
  • Author(s): 吉開泰信
  • Total Pages: 894
  • Publisher: 南江堂
• [Book] 免疫生物学原著第9版 (2018)
  • Author(s): 吉開泰信
  • Total Pages: 355
  • Publisher: 南江堂
  • ISBN: 9784860349172
• [Book] 次世代アジュバント開発のためのメカニズム解明と安全性評価 (2017)
  • Author(s): 吉開泰信
  • Total Pages: 314
  • Publisher: シーエムシー出版
  • ISBN: 9784781312385
• [Book] シンプル免疫学改訂第5版 (2017)
  • Author(s): 吉開泰信
  • Total Pages: 904
  • Publisher: 南江堂
  • ISBN: 9784524254460
• [Book] ウイルスによる膵島細胞障害 -ウイルス糖尿病予防ワクチンの開発は可能か? (2017)
  • Author(s): 永淵正法、勝田仁、三根敬一朗、吉開泰信
  • Total Pages: 236
  • Publisher: 羊土社
• [Book] 次世代アジュバント開発のためのメカニズム解明と安全性評価 アジュバントしてのIL-15 (2017)
  • Author(s): 吉開 泰信
  • Total Pages: 249
  • Publisher: シーエムシー出版
• [Remarks] 徳島大学先端酵素学研究所免疫病態学分野ホームページ
  • URL: https://www.tokushima-autoimmunity.com
• [Remarks] 文部科学省科学研究費補助金 新学術領域研究：ネオ・セルフの生成・機能・構造
  • URL: http://www.tokyo-med.ac.jp/neoself/
• [Remarks] ネオ・セルフの生成・機能・構造
  • URL: http://www.tokyo-med.ac.jp/neoself/