How dendritic cell functional plasticity is maintained? an approach from TSLP signal transduction study

• Project/Area Number: 24591468
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Saga University
• Principal Investigator: ARIMA Kazuhiko 佐賀大学, 医学部, 准教授 (60336112)
• Co-Investigator(Renkei-kenkyūsha): INOUE Hisako 前佐賀大学, 医学部, 助教 (10437816)
• 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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 樹状細胞 / 可塑性 / 細胞内シグナル伝達 / サイトカイン受容体 / TSLP / アレルギー

Outline of Final Research Achievements

Dendritic cells (DCs) have functional plasticity, by which distinct immune responses are induced depending on the nature of infection and inflammation. This phenomenon is granted by the fact that DCs can be differentially activated by distinct activating agents. DC activation through Toll-like receptors results in IL-12 production together with expression of IRF8 and STAT4, critical components of the IL-12 genes transcription. I found that type I interferon (IFN-beta) can induce IRF8 and STAT4 via ERK activation, where Th2-promoting activity of DCs that can be induced by TSLP is irreversibly lost. Thus, the type I IFN is suggested as the major factor that controls DC functional plasticity.

Research Products

• [Journal Article] Periostin contributes to epidermal hyperplasia in psoriasis common to atopic dermatitis (2015)
  • Author(s): Arima K, Ohta S, Takagi A, Shiraishi H, Masuoka M, Ontsuka K, Suto H, Suzuki S, Yamamoto K-i, Ogawa M, Simmons O, Yamaguchi Y, Toda S, Aihara M, Conway SJ, Ikeda S, Izuhara K.
  • Journal Title: Allergology International Volume: 64 Issue: 1 Pages: 41-48
  • DOI: 10.1016/j.alit.2014.06.001
  • NAID: 130004873124
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Periostin controls keratinocyte proliferation and differentiation by interacting with the paracrine IL-1a/IL-6 loop. (2014)
  • Author(s): Taniguchi K, Arima K, Masuoka M, Ohta S, Shiraishi H, Ontsuka K, Suzuki S, Inamitsu M, Yamamoto K-i, Simmons O, Toda S, Conway SJ, Hamasaki Y, Izuhara K.
  • Journal Title: J Invest Dermatol Volume: 134 Issue: 5 Pages: 1295-1304
  • DOI: 10.1038/jid.2013.500
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Periostin in Allergic Inflammation (2014)
  • Author(s): Kenji Izuhara, Kazuhiko Arima, Shoichiro Ohta, Shoichi Suzuki, Masako Inamitsu, and Ken-ichi Yamamoto
  • Journal Title: Allergology International Volume: 63 Issue: 2 Pages: 143-151
  • DOI: 10.2332/allergolint.13-RAI-0663
  • NAID: 130004477217
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function. (2013)
  • Author(s): Voo KS, Bover L, Harline ML, Vien LT, Facchinetti V, Arima K, Kwak LW, Liu YJ
  • Journal Title: Journal of Immunology Volume: 191 Issue: 7 Pages: 3641-3650
  • DOI: 10.4049/jimmunol.1202752
  • Peer Reviewed
• [Journal Article] 基礎研究の炎症疾患診断薬・治療薬開発への応用 (2013)
  • Author(s): 出原 賢治, 太田 昭一郎，有馬 和彦，鈴木 章一，稲光 正子，山本 健一
  • Journal Title: 臨床病理 Volume: 61 Pages: 900-908
• [Journal Article] 気管支喘息の分子病態 (2013)
  • Author(s): 出原 賢治，鈴木 章一，有馬 和彦，稲光 正子，山本 健一，増岡 美穂，太田 昭一郎
  • Journal Title: アレルギー・免疫 Volume: 20 Pages: 958-964
• [Journal Article] オーダーメイド医療を目指したアレルギー疾患における病院診断システムの確立―アトピー性皮膚炎の新規バイオマーカーの同定と血中濃度解析― (2013)
  • Author(s): 太田 昭一郎，谷口 一登，有馬 和彦，鈴木 章一，白石 裕士，増岡 美穂，出原 賢治
  • Journal Title: 臨床病理 Volume: 61 Pages: 247-255
• [Journal Article] Periostin promotes chronic allergic inflammation in response to Th2 cytokines. (2012)
  • Author(s): Masuoka M, Shiraishi H, Ohta S, Suzuki S, Arima K, Aoki S, Toda S, Inagaki N, Kurihara Y, Hayashida S, Takeuchi S, Koike K, Ono J, Noshiro H, Furue M, Conway SJ, Narisawa Y, Izuhara K.
  • Journal Title: J Clin Invest Volume: 122 Issue: 7 Pages: 2590-2600
  • DOI: 10.1172/jci58978
  • Peer Reviewed
• [Journal Article] Periostin, a matricellular protein, accelerates cutaneous wound repair by activating dermal fibroblasts (2012)
  • Author(s): Ontsuka K, Kotobuki Y, Shiraishi H, Serada S, Ohta S, Tanemura A, Yang L, Fujimoto M, Arima K, Suzuki S, Murota H, Toda S, Kudo A, Conway S, Izuhara K, Katayama I, Naka T
  • Journal Title: Experimental Dermatology Volume: 21(5) Issue: 5 Pages: 331-336
  • DOI: 10.1111/j.1600-0625.2012.01454.x
  • Peer Reviewed
• [Journal Article] Periostin Contributes to the Pathogenesis of Atopic Dermatitis by Inducing TSLP Production from Keratinocytes (2012)
  • Author(s): Shiraishi H, Masuoka M, Ohta S, Suzuki S, Arima K, Taniguchi K, Aoki S, Toda S, Yoshimoto T, Inagaki N, Conway SJ, Narisawa Y, Izuhara K
  • Journal Title: Allergology International Volume: 61 Issue: 4 Pages: 563-572
  • DOI: 10.2332/allergolint.10-OA-0297
  • NAID: 130004873049
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Periostin, a matricellular protein, plays a role in the induction of chemokines in pulmonary fibrosis (2012)
  • Author(s): Uchida M, Shiraishi H, Ohta S, Arima K, Taniguchi K, Suzuki S, Okamoto M, Ahlfeld SK, Ohshima K, Kato S, Toda S, Sagara H, Aizawa H, Hoshino T, Conway SJ, Hayashi S, Izuhara K
  • Journal Title: Am J Respir Cell Mol Biol Volume: (In press) Issue: 5 Pages: 677-686
  • DOI: 10.1165/rcmb.2011-0115oc
  • Peer Reviewed
• [Journal Article] 樹状細胞の機能的可塑性 (2012)
  • Author(s): 有馬和彦
  • Journal Title: 臨床免疫・アレルギー科 Volume: 57 Pages: 227-233
• [Journal Article] IL-13 (2012)
  • Author(s): 出原賢治，有馬和彦，鈴木章一，太田昭一郎
  • Journal Title: アレルギー・免疫 Volume: 19 Pages: 1884-1891
• [Journal Article] ペリオスチンによる気管支喘息の病態形成機序． (2012)
  • Author(s): 出原賢治，有馬和彦，白石裕士，鈴木章一，太田昭一郎
  • Journal Title: 臨床免疫・アレルギー科 Volume: 57 Pages: 104-110
  • NAID: 40019192543
• [Journal Article] 気管支喘息におけるサイトカイン研究の最近の話題． (2012)
  • Author(s): 出原賢治，有馬和彦，鈴木章一，白石裕士，太田昭一郎
  • Journal Title: 呼吸と循環 Volume: 60 Pages: 179-187
  • NAID: 40019187927
• [Journal Article] 間質性肺炎の血清マーカーとしてのぺリオスチン． (2012)
  • Author(s): 出原賢治，太田昭一郎，白石裕士，有馬和彦，鈴木章一
  • Journal Title: 検査と技術 Volume: 40 Pages: 157-160
• [Presentation] 2型サイトカインに対する分子標的戦略の基盤 (2015)
  • Author(s): 有馬和彦
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-26 – 2015-05-28
  • Invited
• [Presentation] Periostin contributes to epidermal hyperplasia in psoriasis common to atopic dermatitis (2014)
  • Author(s): Arima K, Ohta S, Shiraishi H, Masuoka M, Ontsuka K, Suzuki S, Sutoh H, Ikeda S, Izuhara K
  • Organizer: 第４３回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] ペリオスチンによるアレルギー性炎症の増幅 (2014)
  • Author(s): 有馬和彦，白石裕士，出原賢治
  • Organizer: 第24回日本サイトメトリー学会学術集会
  • Place of Presentation: 枚方
  • Year and Date: 2014-06-28 – 2014-06-29
  • Invited
• [Presentation] 表皮におけるアレルギー性炎症の増悪化メカニズム． (2013)
  • Author(s): 有馬 和彦，出原 賢治
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] The IL-1alpha/periostin/IL-6 axis contributes to the keratinocyte proliferation and differentiation in atopic dermatitis. (2012)
  • Author(s): Taniguchi K, Arima K, Masuoka M, Shiraishi H, Ohta S, Ontsuka K, Suzuki S, Hamasaki Y , Izuhara K
  • Organizer: 29th Symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Jeju, South Korea
• [Book] Asthma. In: Metabolism of human diseases. (2014)
  • Author(s): Izuhara K, Suzuki S, Arima K, Ohta S, Inamitsu M, Yamamoto K
  • Publisher: Springer
• [Book] 椛島 健治編：病態の理解に向かうアレルギー疾患研究-なぜ、アレルギーが起こるのか? 発症・進展の新概念と臨床への展開．実験医学 増刊 (2013)
  • Author(s): 有馬 和彦，出原 賢治
  • Total Pages: 7
  • Publisher: 羊土社
• [Book] Atopic dermatitis- Disease etiology and clinical management. (2012)
  • Author(s): Izuhara K, Shiraishi H, Ohta S, Arima K, Suzuki S.
  • Total Pages: 12
  • Publisher: INTECH Ltd.
• [Book] Translational Science: from basic to clinical immunology and allergy (2012)
  • Author(s): Izuhara K, Masuoka M, Shiraishi H, Ohta S, Suzuki S, Arima K.
  • Total Pages: 4
  • Publisher: Pacini editore
• [Book] サイトカインのすべて(完全改訂版)（臨床免疫・アレルギー科第57巻特別増刊号） (2012)
  • Author(s): 出原賢治、有馬和彦、鈴木章一、白石裕士、太田昭一郎
  • Total Pages: 6
  • Publisher: 科学評論社
• [Book] サイトカインのすべて(完全改訂版)（臨床免疫・アレルギー科第57巻特別増刊号） (2012)
  • Author(s): 有馬和彦、渡部則彦
  • Total Pages: 9
  • Publisher: 科学評論社
• [Remarks] 佐賀大学医学部分子生命科学講座分子医化学分野
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/index.php
• [Remarks] 佐賀大学医学部分子生命科学講座分子医化学分野業績一覧
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/publications.html
• [Remarks] 佐賀大学医学部分子生命科学講座分子医化学分野ホームページ/研究内容
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/research.html
• [Remarks] 佐賀大学医学部分子生命科学講座分子医化学分野ホームページ/研究業績
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/publications.html
• [Remarks] 佐賀大学医学部分子生命科学講座分子医化学分野ホームページ
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/index.php
• [Patent(Industrial Property Rights)] ペリオスチンの特定領域に結合する抗体及びこれを用いたペリオスチンの測定方法 (2014)
  • Inventor(s): 出原賢治，有馬和彦他
  • Industrial Property Rights Holder: 出原賢治，有馬和彦他
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-02-26
• [Patent(Industrial Property Rights)] 眼科疾患を除くペリオスチン発現に起因する疾患用医薬、およびその用途 (2013)
  • Inventor(s): 出原賢治，有馬和彦他
  • Industrial Property Rights Holder: 出原賢治，有馬和彦他
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-202051
  • Filing Date: 2013-09-27
• [Patent(Industrial Property Rights)] アトピー性角結膜炎の検出方法 (2013)
  • Inventor(s): 出原賢治，有馬和彦他
  • Industrial Property Rights Holder: 出原賢治，有馬和彦他
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-218612
  • Filing Date: 2013-10-21
• [Patent(Industrial Property Rights)] 気管支喘息の予防又は治療薬及びそのスクリーニング方法 (2013)
  • Inventor(s): 出原賢治、太田昭一郎，有馬和彦，鈴木章一ら
  • Industrial Property Rights Holder: 佐賀大学、山形大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-01-22
  • Overseas
• [Patent(Industrial Property Rights)] ペリオスチンの特定領域に結合する抗体及びこれを用いたペリオスチンの測定方法 (2012)
  • Inventor(s): 出原賢治、太田昭一郎，有馬和彦，鈴木章一ら
  • Industrial Property Rights Holder: 佐賀大学，久留米大学，株式会社シノテスト
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-09-06
  • Overseas
• [Patent(Industrial Property Rights)] 慢性副鼻腔炎の検出方法 (2012)
  • Inventor(s): 出原賢治、太田昭一郎，有馬和彦，鈴木章一ら
  • Industrial Property Rights Holder: 佐賀大学、山形大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-10-30
  • Overseas