Effects of innate immune activation induced by infection or tissue damage on the development of thyroid autoimmunity

• Project/Area Number: 24591375
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: SUZUKI Koichi 国立感染症研究所, 感染制御部, 室長 (20206478)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 甲状腺 / 自然免疫 / dsDNA / サイログロブリン / 獲得免疫

Outline of Final Research Achievements

Rat thyroid FRTL-5 cells or primary culture of mouse thyroid cells were stimulated by electric pulse to induce cell damage, or transfected with human herpes virus genomic DNA or synthetic double-stranded polynuclerotides. After these treatments, expression of series of genes essential for innate and acquired immune responses was induced. However, thyroglobulin gene expression and iodine uptake were suppressed by these treatments. These results suggest that when immune functions of thyroid cells are activated upon infection or tissue damage, thyroid hormone biosynthesis may be suppressed. Further studies are needed to confirm this possibility.

Research Products

• [Journal Article] Iodine excess as an environmental risk factor for autoimmune thyroid disease (2014)
  • Author(s): Luo Y, Kawashima A, Ishido Y, Yoshihara A, Oda K, Hiroi N, Ito T, Ishii N and Suzuki K
  • Journal Title: Int J Mol Sci Volume: 15 Issue: 7 Pages: 12895
  • DOI: 10.3390/ijms150712895
  • Peer Reviewed / Open Access
• [Journal Article] The emerging roles of thyroglobulin (2014)
  • Author(s): Luo Y, Ishido Y, Hiroi N, Ishii N and Suzuki K
  • Journal Title: Advances in Endocrinology Volume: 2014 Pages: 189194-189194
  • DOI: 10.1155/2014/189194
  • Peer Reviewed / Open Access
• [Journal Article] Intrinsic regulation of thyroid function by thyroglobulin (2014)
  • Author(s): Sellitti DF, Suzuki K
  • Journal Title: Thyroid Volume: 24 Issue: 4 Pages: 625
  • DOI: 10.1089/thy.2013.0344
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Thyroglobulin suppresses thyroid-specific gene expression in cultures of normal but not neoplastic human thyroid follicular cells (2014)
  • Author(s): Ishido Y, Yamazaki K, Kammori M, Sugishita Y, Luo Y, Yamada E, Yamada T, Sellitti DF, Suzuki K
  • Journal Title: J Clin Endocrinol Metab Volume: 99 Issue: 4 Pages: E694-E702
  • DOI: 10.1210/jc.2013-3682
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Thyroglobulin increases thyroid cell proliferation via the suppression of specific MicroRNAs (2014)
  • Author(s): Akama T, Luo Y, Sellitti DF, Kawashima A, Tanigawa K, Yoshihara A, Ishido Y, Nakamura K, Tanoue A, Suzuki K
  • Journal Title: Mol Endocrinol Volume: 28 Issue: 3 Pages: 368
  • DOI: 10.1210/me.2013-1266
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Demonstration of innate immune responses in the thyroid gland: Potential to sense danger and a possible trigger for autoimmune reactions (2013)
  • Author(s): Kawashima A, Yamazaki K, Hara T, Akama T, Yoshihara A, Sue M, Tanigawa K, Wu H, Ishido Y, Takeshita F, Ishii N, Sato K, Suzuki K
  • Journal Title: Thyroid Volume: 23 Issue: 4 Pages: 477
  • DOI: 10.1089/thy.2011.0480
  • Peer Reviewed
• [Journal Article] Role of extrachromosomal histone H2B on recognition of DNA viruses and cell damage (2013)
  • Author(s): Kobiyama K, Kawashima A, Jounai N, Takeshita F, Ishii KJ, Ito T, Suzuki K
  • Journal Title: Front Genet Volume: 4 Issue: MAY Pages: 1-7
  • DOI: 10.3389/fgene.2013.00091
  • Peer Reviewed
• [Journal Article] 橋本病における遺伝子発現異常と病態 (2013)
  • Author(s): 木村 博昭, 鈴木 幸一
  • Journal Title: カレントテラピー Volume: 31 Pages: 71-75
• [Journal Article] 橋本病の病因 (2013)
  • Author(s): 鈴木 幸一, 木村 博昭
  • Journal Title: 日本甲状腺学会雑誌 Volume: 4 Pages: 14-18
• [Journal Article] 損傷細胞由来DNAと自己免疫疾患 (2013)
  • Author(s): 74. 鈴木 幸一
  • Journal Title: 臨床免疫・アレルギー科 Volume: 60 Pages: 247-257
• [Journal Article] Thyroglobulin (Tg) activates MAPK pathway to induce thyroid cell growth in the absence of TSH, insulin and serum (2013)
  • Author(s): Sue M, Hayashi M, Kawashima A, Akama T, Tanigawa K, Yoshihara A, Hara T, Ishido Y, Ito T, Takahashi S-I, Ishii N and Suzuki K
  • Journal Title: Biochem Biophys Res Commun Volume: 420 Issue: 3 Pages: 611
  • DOI: 10.1016/j.bbrc.2012.03.046
  • Peer Reviewed
• [Journal Article] Phosphatidylinositol 3-kinase-binding protein, PI3KAP/XB130, is required for cAMP-induced amplification of IGF mitogenic activity in FRTL-5 thyroid cells (2012)
  • Author(s): Yamanaka D, Akama T, Fukushima T, Nedachi T, Kawasaki C, Chida K, Minami S, Suzuki K, Hakuno F, Takahashi S-I.
  • Journal Title: Mol Endocrinol Volume: 26 Issue: 6 Pages: 1043
  • DOI: 10.1210/me.2011-1349
  • Peer Reviewed
• [Journal Article] Propylthiouracil increases sodium/iodide symporter gene expression and iodide uptake in rat thyroid cells in the absence of TSH (2012)
  • Author(s): Sue M, Akama T, Kawashima A, Nakamura H, Hara T, Tanigawa K, Wu H, Yoshihara A, Ishido Y, Hiroi N, Yoshino G, Kohn LD, Ishii N, and Suzuki K
  • Journal Title: Thyroid Volume: 22 Issue: 8 Pages: 844
  • DOI: 10.1089/thy.2011.0290
• [Journal Article] Regulation of dual oxidase expression and H₂O₂ production by thyroglobulin (2012)
  • Author(s): Yoshihara A, Hara T, Kawashima A, Akama T, Tanigawa K, Wu H, Sue M, Ishido Y, Hiroi N, Ishii N, Yoshino G, Suzuki K
  • Journal Title: Thyroid Volume: 22 Issue: 10 Pages: 1054
  • DOI: 10.1089/thy.2012.0003
  • Peer Reviewed
• [Journal Article] Identification of microRNAs that mediate thyroid cell growth induced by TSH (2011)
  • Author(s): Akama T, Sue M, Kawashima A, Wu H, Tanigawa K, Suzuki S, Hayashi M, Yoshihara A, Ishido Y, Ishii N, Suzuki K
  • Journal Title: Mol Endocrinol Volume: 26 Issue: 3 Pages: 493
  • DOI: 10.1210/me.2011-1004
  • Peer Reviewed
• [Presentation] 脂質ラフト構造がサイログロブリン(Tg)による遺伝子発現調節機構を介在する (2014)
  • Author(s): Yuqian Luo、赤間 剛、岡山明子、石藤雄子、平野 久、鈴木幸一
  • Organizer: 第87回日本内分泌学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Thyroglobulin (Tg)は細胞膜のlipid raftを介して甲状腺機能遺伝子発現を調節する (2014)
  • Author(s): Yuqian Luo、赤間 剛、岡山明子、石藤雄子、平野 久、鈴木幸一
  • Organizer: 第30回甲状腺病態生理研究会
  • Place of Presentation: 東京
• [Presentation] ヒト正常甲状腺細胞はサイログロブリン(Tg)によるnegative feedback機構で機能遺伝子発現が抑制されるが腫瘍はTgの影響を受けない (2013)
  • Author(s): 石藤雄子、山崎和子、神森 眞、杉下佳之、Yuqian Luo、山田恵美子、山田 哲、鈴木幸一
  • Organizer: 第56回日本甲状腺学会
  • Place of Presentation: 和歌山市
• [Presentation] サイログロブリンはmiRNAの発現抑制を通じて細胞増殖関連遺伝子を誘導し甲状腺細胞を増殖させる (2012)
  • Author(s): 赤間剛、鈴木幸一
  • Organizer: 第85回日本内分泌学会
  • Place of Presentation: 名古屋市
• [Presentation] 自己免疫性甲状腺炎の病態における免疫プロテアソームの関与 (2012)
  • Author(s): 木村博昭、鈴木幸一、高橋将文、Patrizio Caturegli
  • Organizer: 第85回日本内分泌学会、シンポジウム
  • Place of Presentation: 名古屋市
  • Invited
• [Presentation] Thyroglobulin induces thyroid cell growth through suppression of miR-16 and miR-195 (2012)
  • Author(s): Akama, T. Hara T, D. Yang, A. Kawashima, A. Yoshihara, M. Sue, K. Tanigawa, H. Wu, Y. Ishido, N. Ishii and K. Suzuki
  • Organizer: 15th International Congress of Endocrinology
  • Place of Presentation: イタリア
• [Presentation] 甲状腺特異的IFNγトランスジェニックマウスのHurthle細胞の出現と甲状腺機能低下は相関する (2012)
  • Author(s): 木村博昭、岩間信太郎、鈴木幸一、高橋将文、Patrizio Cturegli
  • Organizer: 第53回日本甲状腺学会
  • Place of Presentation: 福岡市
• [Presentation] 自己免疫疾患発症に関わる甲状腺細胞が持つ自然免疫活性化機構の検討 (2012)
  • Author(s): 川島晃、山崎和子、原武史、赤間剛、須江麻里子、吉原彩、谷川和也、石藤雄子、木村博昭、佐藤幹二、鈴木幸一
  • Organizer: 第53回日本甲状腺学会
  • Place of Presentation: 福岡市
• [Presentation] Thyrocyte-adipose tissue interaction: A perspective on thyroid-adipose axis (2012)
  • Author(s): 山本美保子、小池英介、鈴木幸一、米満伸久、小池則雅、戸田修二
  • Organizer: 第53回日本甲状腺学会、基礎甲状腺学セミナー
  • Place of Presentation: 福岡市
  • Invited
• [Presentation] Reevaluation of mouse models of Hashimoto’s thyroiditis (2012)
  • Author(s): H. Kimura, K. Suzuki, S. Iwama, N.R. Rose, M. Takahashi, P. Caturegli
  • Organizer: 第53回日本甲状腺学会、橋本病100周年記念国際シンポジウムI「甲状腺と自己免疫」
  • Place of Presentation: 福岡市
  • Invited