Elucidation of the role of calcium signaling on peripheral immune tolerance.

• Project/Area Number: 23590565
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyushu University (2013); Tokyo Medical and Dental University (2011-2012)
• Principal Investigator: OH-HORA Masatsugu 九州大学, 生体防御医学研究所, 准教授 (40351506)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 制御性T細胞 / カルシウムシグナル / 樹状細胞 / 免疫寛容 / カルシウム / サイトカイン

Research Abstract

To elucidate the mechanism of immune tolerance in the periphery, we analyzed the role of calcium signaling in regulatory T cells and dendritic cells using cell-type specific Stim-deficient mice. In the absence of store-operated calcium entry in T cells, regulatory T cell development in the thymus was blocked at the transition of precursor cells to mature regulatory T cells. As a result, peripheral immune tolerance was disrupted. Block of calcium signaling in dendritic cells resulted in mild impairment of immune response to antigen but not of peripheral immune tolerance.

Research Products

• [Journal Article] Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. (2014)
  • Author(s): Komatsu, N., Okamoto, K., Sawa, S., Nakashima, T., Oh-hora, M., Kodama, T., Tanaka, S., Bluestone, JA. and Takayanagi, H.
  • Journal Title: Nature Medicine Volume: 20 Issue: 1 Pages: 62-68
  • DOI: 10.1038/nm.3432
  • Peer Reviewed / Open Access
• [Journal Article] Agonist-selected T cell development requires strong T cell receptor signaling and store-operated calcium entry (2013)
  • Author(s): Oh-hora, M., et al.
  • Journal Title: Immunity Volume: 38 Issue: 5 Pages: 1-15
  • DOI: 10.1016/j.immuni.2013.02.008
  • Peer Reviewed
• [Journal Article] STIM1 juxtaposes ER to phagosomes, generating Ca(2+) hotspots that boost phagocytosis (2012)
  • Author(s): Nunes, P., et al.
  • Journal Title: Curr Biol Volume: 22 Issue: 21 Pages: 1990-1997
  • DOI: 10.1016/j.cub.2012.08.049
  • Peer Reviewed
• [Journal Article] STIM1 and STIM2 protein deficiency in T lymphocytes underlies development of the exocrine gland autoimmune disease, Sjogren's syndrome (2012)
  • Author(s): Cheng, KT., et al
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Issue: 36 Pages: 14544-14549
  • DOI: 10.1073/pnas.1207354109
  • Peer Reviewed
• [Journal Article] STIM1-Ca(2+) signaling is required for the hypertrophic growth of skeletal muscle in mice (2012)
  • Author(s): Li, T., et al.
  • Journal Title: Mol Cell Biol Volume: 32 Issue: 15 Pages: 3009-3017
  • DOI: 10.1128/mcb.06599-11
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): Nakashima, T., et al
  • Journal Title: Nat Med Volume: 17 Issue: 10 Pages: 1231-1234
  • DOI: 10.1038/nm.2452
  • Peer Reviewed
• [Journal Article] Stanninocalcin 2 is a negative modulator of store-operated calcium entry (2011)
  • Author(s): Zeiger, W., Ito, D., Swetlik, C., Oh-hora, M., Villereal, ML. and Thinakaran, G.
  • Journal Title: Mol Cell Biol Volume: 31 Issue: 18 Pages: 3710-3722
  • DOI: 10.1128/mcb.05140-11
  • Peer Reviewed
• [Journal Article] Stanniocalcin 2 is a negative modulator of store-operated calcium entry (2011)
  • Author(s): Zeiger, W., et al.
  • Journal Title: Mol Cell Biol Volume: 31 Pages: 3710-3722
  • Peer Reviewed
• [Presentation] ストア作動性カルシウム流入の異常による疾患発症メカニズム (2014)
  • Author(s): 大洞将嗣、小松紀子、Anjana Rao、高柳広
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] ストア作動性カルシウム流入による免疫制御 (2014)
  • Author(s): 大洞将嗣
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島
• [Presentation] NFAT2-dependent IL-4-producing follicular helper T cells is a critical factor in T_H2 inflammation by the lack of store-operated calcium entry (2014)
  • Author(s): Oh-hora, M., Lu, X. and Yamasaki, S.
  • Organizer: Keystone Symposia
  • Place of Presentation: Vancouver, Canada
• [Presentation] NFAT2-dependent IL-4-producing follicular helper T cells is a critical factor in Th2 inflammation by the lack of store-operated calcium entry. (2014)
  • Author(s): Masatsugu Oh-hora, Xiuyuan Lu, Sho Yamasaki
  • Organizer: Keystone Symposia
  • Place of Presentation: Vancouver, Canada
• [Presentation] ストア作動性カルシウム流入の異常による疾患発症のメカニズム (2014)
  • Author(s): 9. 大洞将嗣, 小松紀子, Anjana Rao, 高柳広
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] T細胞分化とストア作動性カルシウム流入 (2013)
  • Author(s): 大洞将嗣、小松紀子、Anjana Rao、高柳広
  • Organizer: 第22回東京免疫フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2013-03-14
• [Presentation] Search for downstream targets of protein kinase D that is critical for T cell development (2013)
  • Author(s): Ishikawa, E., Oh-hora, M., Kurosaki, T., Saito, T. and Yamasaki, S.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] STIM1-mediated store operated Ca^<2+> entry is essential for basophil recruitment in IgE-mediated chronic allergic inflammation (2013)
  • Author(s): Yoshikawa, S., Oh-hora, M., Miyake, K., Li, L., Ohta, T., Adachi, T., Horiguchi, K., Kawano, Y. and Karasuyama, H.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Store-operated calcium entry and T cell development (2013)
  • Author(s): Oh-hora, M., Komatsu, N., Rao, A. and Takayanagi, H.
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 千葉
• [Presentation] STIM1を介したストア作動性カルシウム流入は好塩基球の脱顆粒および炎症局所への浸潤に重要である (2013)
  • Author(s): 三宅健介、吉川宗一郎、大洞将嗣、烏山一
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
• [Presentation] Store-operated calcium entry is crucial for the development of agonist-selected T cells (2013)
  • Author(s): Oh-hora, M., Komatsu, N., Rao, A. and Takayanagi, H.
  • Organizer: FASEB Science Research Conference
  • Place of Presentation: Nassau, Bahamas
• [Presentation] Strong TCR/calcium signaling specifically controls the development of regulatory T cell subsets (2013)
  • Author(s): 大洞将嗣、小松紀子、Stefan Feske、堀昌平、Anjana Rao、高柳広
  • Organizer: Frontiers in Immunology and Inflammation
  • Place of Presentation: 東京
• [Presentation] Store-operated calcium entry is crucial for the development of agonist-selected T cells. (2013)
  • Author(s): Masatsugu Oh-hora, Noriko Komatsu, Anjana Rao, Hiroshi Takayanagi
  • Organizer: FASEB Science Research Conference
  • Place of Presentation: Nassau, Bahamas
• [Presentation] STIM1を介したストア作動性カルシウム流入は好塩基球の脱下流および炎症局所への浸潤に重要である (2013)
  • Author(s): 三宅健介, 吉川宗一郎, 大洞将嗣, 烏山一
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
• [Presentation] Store-operated calcium entry and T cell development. (2013)
  • Author(s): Masatsugu Oh-hora, Noriko Komatsu, Anjana Rao, Hiroshi Takayanagi
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] STIM1-mediated store operated Ca2+ entry is essential for basophil recruitment in IgE-mediated chronic allergic inflammation. (2013)
  • Author(s): Soichiro Yoshikawa, Masatsugu Oh-hora, Kensuke Miyake, Lihua Li, Takuya Ohta, Takahiro Adachi, Kayo Horiguchi, Yohei Kawano, Hajime Karasuyama
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Search for downstream targets of protein kinase D that is critical for T cell development. (2013)
  • Author(s): Eri Ishikawa, Masatsugu Oh-hora, Tomohiro Kurosaki, Takasi Saito, Sho Yamasaki
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] T細胞分化とストア作動性カルシウム流入 (2013)
  • Author(s): 大洞将嗣、小松紀子、Anjana Rao、高柳広
  • Organizer: 第２２回東京免疫フォーラム
  • Place of Presentation: 東京
  • Invited
• [Presentation] STIM依存性カルシウム流入によるT細胞の分化制御 (2012)
  • Author(s): 大洞将嗣
  • Organizer: 第122回小児血液腫瘍懇話会
  • Place of Presentation: 東京
  • Year and Date: 2012-11-02
• [Presentation] 小胞体カルシウムセンサーSTIMによるT細胞分化制御 (2012)
  • Author(s): 大洞将嗣
  • Organizer: 第8回骨免疫ワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2012-11-02
• [Presentation] Agonist-selected T cell development requires strong TCR/calcium signaling (2012)
  • Author(s): Oh-hora, M.,Komastu, N., Feske, S.,Hori, S., Rao, A. and Takayanagi, H.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] STIM1-mediated store operated Ca^2+ entry is essential for basophil recruitment in IgE-mediated chronic allergic inflammation (2012)
  • Author(s): Yoshikawa, S., Egawa, M., Oh-hora, M., Adachi, T., Horiguchi, K., Li, L., Ohta, T., Kawano, Y., Minagishi, Y. and Karasuyama, H.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Agonist-selected T cell development requires strong TCR/calcium signaling (2012)
  • Author(s): 大洞将嗣、小松紀子、Stefan Feske、堀昌平、Anjana Rao、高柳広
  • Organizer: 第４１回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Agonist-selected T cell development requires strong TCR/calcium signaling (2012)
  • Author(s): 大洞将嗣、小松紀子、高柳広
  • Organizer: 第２２回KTCC
  • Place of Presentation: 京都
• [Presentation] Agonist-selected T cell development requires strong TCR/calcium signaling (2011)
  • Author(s): 大洞将嗣、小松紀子、高柳広
  • Organizer: 第22回Kyoto T cell conference (KTCC)
  • Place of Presentation: 京都
  • Year and Date: 2011-06-10
• [Presentation] Lineage-specific requirement of store-operated calcium entry in T cell lineage development (2011)
  • Author(s): 大洞 将嗣
  • Organizer: 第21回KTCC
  • Place of Presentation: 京都
• [Presentation] 小胞体カルシウムセンサーSTIM によるT細胞分化制御
  • Author(s): 大洞将嗣
  • Organizer: 第８回骨免疫ワークショップ
  • Place of Presentation: 東京
  • Invited
• [Book] イラストで徹底理解するシグナル伝達キーワード事典 (2012)
  • Author(s): 大洞将嗣、高柳広
  • Publisher: 羊土社
• [Book] イラストで徹底理解するシグナル伝達キーワード事典 (2012)
  • Author(s): 大洞将嗣、黒崎知博
  • Publisher: 羊土社
• [Book] イラストで徹底理解する シグナル伝達キーワード事典 (2012)
  • Author(s): 大洞将嗣、高柳広
  • Publisher: 羊土社
• [Book] イラストで徹底理解する シグナル伝達キーワード事典 (2012)
  • Author(s): 大洞将嗣、黒崎知博
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/mib/divisions/summary_in_mi.pdf
• [Remarks] 過剰な免疫反応にブレーキをかけるＴ細胞が作られる共通の仕組みを解明
  • URL: http://www.jst.go.jp/pr/announce/20130315/