Analysis of negative selection regulated by medullary thymic epithelial cells

• Project/Area Number: 25860363
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: The University of Tokushima
• Principal Investigator: MOURI Yasuhiro 徳島大学, 疾患酵素学研究センター, 助教 (80464353)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: Aire / 負の選択 / 胸腺上皮細胞 / AIRE / mTEC / 自己免疫 / 胸腺

Outline of Final Research Achievements

We investigated a role of Aire, expressed in medullary thymic epithelial cells, in negative selection using neo self-antigen Tg models. Self-antigens expressed in thymic epithelial cells are (1)directly presented by thymic epithelial cells or (2)indirectly presented by BM-derived antigen presenting cells (BM-APC) such as dendritic cells. Our results suggested Aire is needed in (2)indirect presentation by BM-APC but not (1)direct presentation by thymic epithelial cells. It is thought that Aire regulates antigen presentation by BM-APCs but not thymic epithelial cells in negative selection.

Research Products

• [Journal Article] Aire Expression Is Inherent to Most Medullary Thymic Epithelial Cells during Their Differentiation Program. (2015)
  • Author(s): Kawano H, Nishijima H, Morimoto J, Hirota F, Morita R, Mouri Y, Nishioka Y, Matsumoto M.
  • Journal Title: Journal of Immunology Volume: 195 Issue: 11 Pages: 5149-5158
  • DOI: 10.4049/jimmunol.1501000
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ectopic Aire expression in 1 the thymic cortex reveals inherent properties of Aire as a tolerogenic factor within the medulla (2015)
  • Author(s): Nishijima H, Kitano S, Miyachi H, Morimoto J, Kawano H, Hirota F, Morita R, Mouri Y, Masuda K, Imoto I, Ikuta K, Matsumoto M.
  • Journal Title: J Immunol Volume: 195 Issue: 10 Pages: 4641-4649
  • DOI: 10.4049/jimmunol.1501026
  • Peer Reviewed / Open Access
• [Journal Article] NIK in thymic stroma establishes central tolerance by orchestrating cross-talk with not only thymocytes but also dendritic cells (2014)
  • Author(s): Mouri, Y., Nishijima, H., Kawano, H., Hirota, F., Sakaguchi, N., Morimoto, J., Matsumoto, M.
  • Journal Title: J. Immunol. Volume: 193 Issue: 9 Pages: 4356-4367
  • DOI: 10.4049/jimmunol.1400389
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program (2014)
  • Author(s): Nishikawa, Y., Nishijima, H., Matsumoto, M., Morimoto, J., Hirota, F., Takahashi, S., Luche, H., Fehling, H.J., Mouri, Y., Matsumoto, M.
  • Journal Title: J. Immunol Volume: 192 Issue: 6 Pages: 2585-2592
  • DOI: 10.4049/jimmunol.1302786
  • Peer Reviewed / Open Access
• [Journal Article] Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling (2013)
  • Author(s): Yoshida S, Aihara K, Ikeda Y, Sumitomo-Ueda Y, Uemoto R, Ishikawa K, Ise T, Yagi S, Iwase T, Mouri Y, Sakari M, Matsumoto T, Takeyama K, Akaike M, Matsumoto M, Sata M, Walsh K, Kato S, Matsumoto T.
  • Journal Title: Circulation Volume: 128 Issue: 1 Pages: 60-71
  • DOI: 10.1161/circulationaha.113.001533
  • Peer Reviewed
• [Journal Article] Which model better fits the role of Aire in the establishment of self-tolerance: the transcription model or the maturation model? (2013)
  • Author(s): Matsumoto, M., Nishikawa, Y., Nishijima, H., Morimoto, J., Matsumoto, M., Mouri, Y.
  • Journal Title: Front. Immunol. Volume: 4 Pages: 1-4
  • DOI: 10.3389/fimmu.2013.00210
  • Peer Reviewed
• [Presentation] Unexpected disturbance of the development of medullary thymic epithelial cells at immature stages by the long-term ablation of mature Aire-expressing cells (2014)
  • Author(s): Kawano, H., Morimoto, J., Mouri, Y., Nishijima, H., Nishioka, Y., Matsumoto, M.
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Approaches to identify Aire-regulated non-tissue-restricted antigen genes by the ectopic expression of Aire in thymic cortex (2014)
  • Author(s): Nishijima, H., Morimoto, J., Mouri, Y., Kawano, H., Ikuta, K., Matsumoto, M.
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Ectopic Aire expression in thymic cortex reveals inherent properties of Aire as a stromal factor for medullary thymic microenvironment (2014)
  • Author(s): Nishijima, H., Morimoto, J., Kawano, H., Mouri, Y., Ikuta, K., Matsumoto, M.
  • Organizer: ThymOz 7
  • Place of Presentation: Heron Island (Australia)
  • Year and Date: 2014-04-02 – 2014-04-07
• [Presentation] Temporal lineage tracing of Aire-expressing cells reveals a requirement of Aire for their full maturation program (2013)
  • Author(s): Nishikawa, Y., Mouri, Y., Nishijima, H., Matsumoto, M.
  • Organizer: Controversies in Rheumatology and Autoimmunity
  • Place of Presentation: Hotel Novotel Budapest City（Hungary）
• [Presentation] Temporal fate-mapping study reveals essential roles of Aire in the maturation program of Aire-expressing cell lineage (2013)
  • Author(s): Matsumoto, M., Nishikawa, Y., Mouri, Y., Nishijima, H.
  • Organizer: IMMUNOLOGY 2013-AAI Annual Meeting
  • Place of Presentation: Hawaii Convention Center（USA）
• [Presentation] AIRE遺伝子を導入したHeLa細胞における細胞周期依存的なAIREタンパク質のリン酸化 (2013)
  • Author(s): 西嶋 仁、毛利安宏、西川裕美子、松本 満
  • Organizer: 第54回日本生化学中国・四国支部例会
  • Place of Presentation: 徳島大学大塚講堂（徳島県）
• [Presentation] Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program (2013)
  • Author(s): Matsumoto, M., Nishikawa, Y., Nishijima, H., Matsumoto, M., Morimoto, J., Hirota, F., Takahashi, S., Luche, H., Fehling, H.J., Mouri, Y.
  • Organizer: The 6th International Workshop of Kyoto T Cell Conference
  • Place of Presentation: 芝蘭会館（京都府）
• [Presentation] Temporal lineage tracing of Aire-expressing cells reveals a requirement of Aire for their maturation program
  • Author(s): Matsumoto, M., Nishikawa, Y., Mouri, Y., Nishijima, H.
  • Organizer: 15th ICI2013
  • Place of Presentation: MiCo Milano Congressi（Italy）
• [Presentation] Requirement of Aire expression within thymic medulla but not cortex for establishing self-tolerance
  • Author(s): Nishijima, H., Morimoto, J., Mouri, Y., Nishikawa, Y., Ikuta, K., Matsumoto, M.
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ（千葉県）