Exploration of signal transduction mechanism of TSLP aiming at developing a novel therapy for allergic disorders

• Project/Area Number: 22790935
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• 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, 講師 (60336112)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アレルギー学 / サイトカイン / アレルギー疾患 / TSLP / サイトカイン受容体 / 樹状細胞 / 細胞内シグナル伝達

Research Abstract

Thymic stromal lymphopoietin(TSLP) is a cytokine that plays an important role in the development of allergic inflammation. It was shown to activate human dendritic cells to promote Th2-type immune response. We examined the detailed signal transduction mechanism of TSLP. The multiple signal pathways activated by TSLP were selectively down-regulated by the Th1-inducing agents such as TLR ligands. Furthermore, we successfully established a cell line that demonstrates activation of the similar signal pathways by TSLP to those in dendritic cells. This cell line will be of great help in analyzing biochemical properties of the TSLP signal transduction

Research Products

• [Journal Article] Cellular and molecular mechanisms of TSLP function in human allergic disorders-TSLP programs the" Th2 code" in dendritic cells- (2012)
  • Author(s): Ito T, Liu Y-J, Arima K
  • Journal Title: Allergol Int Volume: 61 Pages: 35-43
  • NAID: 130004873041
• [Journal Article] Thymic stromal lymphopoietin programs the" allergy code" in dendritic cells (2012)
  • Author(s): Arima K, Liu Y-J
  • Journal Title: Inflamm Regen Volume: 32 Pages: 23-31
  • NAID: 130004482289
• [Journal Article] 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. Periostin
  • Journal Title: Am J Respir Cell Mol Biol Volume: (Epub ahead of print)
• [Journal Article] 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 SJ, Narisawa Y, Katayama I, Izuhara K, Naka T. Periostin
  • Journal Title: Exp Dermatol Volume: 21 Pages: 331-336
• [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] ぺ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, 鈴木章一, 白石裕士, 太田昭一郎
  • Journal Title: 臨床免疫・アレルギー科 Volume: 57 Pages: 104-110
• [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
• [Journal Article] Cellular and Molecular Mechanisms of TSLP Function in Human Allergic Disorders - TSLP Programs the "Th2 code" in Dendritic Cells (2012)
  • Author(s): Tomoki Ito, et al
  • Journal Title: Allergology International Volume: 61 Issue: 1 Pages: 35-43
  • DOI: 10.2332/allergolint.11-RAI-0376
  • NAID: 130004873041
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Thymic stromal lymphopoietin programs the "allergy code" in dendritic cells (2012)
  • Author(s): Arima K, Liu YJ
  • Journal Title: Inflammation and Regeneration Volume: 32 Pages: 23-31
  • NAID: 130004482289
  • 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] 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] 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, 鈴木章一, 白石裕士, 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] 間質性肺炎の血清マーカーとしてのペリオスチン (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
• [Journal Article] アレルギー発症におけるthymic stromal lymphopoietin(TSLP)の作用 (2011)
  • Author(s): 有馬和彦
  • Journal Title: 生化学 Volume: 83 Pages: 1109-1113
  • NAID: 10030345925
• [Journal Article] アレルギー発症におけるthymic stromal lymphopoietin (TSLP)の作用 (2011)
  • Author(s): 有馬和彦
  • Journal Title: 生化学 Volume: 83 Pages: 1109-1113
  • NAID: 10030345925
  • Peer Reviewed
• [Journal Article] Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of forkhead box P3^+ regulatory T cells in human thymus (2010)
  • Author(s): Hanabuchi S, Ito T, Park WR, Watanabe N, Shaw JL, Roman E, Arima K, Wang YH, Voo KS, Cao W, Liu YJ
  • Journal Title: J Immunol Volume: 184 Pages: 2999-3007
• [Journal Article] Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells (2010)
  • Author(s): Matsushita H, Ohta S, Shiraishi H, Suzuki S, Arima K, Toda S, Tanaka H, Nagai H, Kimoto M, Inokuchi A, Izuhara K
  • Journal Title: Int Immunol Volume: 22 Pages: 739-747
  • NAID: 10030913704
• [Journal Article] Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells. (2010)
  • Author(s): Matsushita H, Ohta S, Shiraishi H, Suzuki S, Arima K, Toda S, Tanaka H, Nagai H, Kimoto M, Inokuchi A, Izuhara K
  • Journal Title: International Immunology Volume: 22 Pages: 739-747
  • NAID: 10030913704
  • Peer Reviewed
• [Presentation] ぺリオスチンはインターロイキン6産生を介して表皮角化細胞の増殖・分化に関与する (2011)
  • Author(s): Taniguchi K, Arima K, Masuoka M, Shiraishi H, Ohta S, Ontsuka K, Suzuki S, Conway SJ, Izuhara K
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張市,千葉県
  • Year and Date: 2011-11-27
• [Presentation] ペリオスチンはインターロイキン6産生を介して表皮角化細胞の増殖・分化に関与する (2011)
  • Author(s): Taniguchi K, Arima K, Masuoka M, Shiraishi H, Ohta S, Ontsuka K, Suzuki S, Conway SJ, Izuhara K
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張市,千葉県
  • Year and Date: 2011-11-27
• [Presentation] 細胞外マトリックスを介したアトピー性皮膚炎の病態形成(シンポジスト) (2011)
  • Author(s): 有馬和彦, 出原賢治
  • Organizer: 第61回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京都
  • Year and Date: 2011-11-11
• [Presentation] 細胞外マトリックスを介したアトピー性皮膚炎の病態形成 (2011)
  • Author(s): 有馬和彦, 出原賢治
  • Organizer: 第61回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京都(招待講演)
  • Year and Date: 2011-11-11
• [Presentation] Distinct signal codes generate dendritic cell functional plasticity (2011)
  • Author(s): Arima K, Watanabe N, Hanabuchi S, Chang M, Sun S-C, Liu Y-J
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸市,兵庫県
  • Year and Date: 2011-08-24
• [Presentation] Development of combined measurement of squamous cell carcinoma antigens 1 and 2 as a potential companion diagnostic for anti-IL-4/ IL-13 therapies in allergic diseases (2011)
  • Author(s): Ohta S, Shibata R, Nakao Y, Azuma Y, Taniguchi K, Arima K Suzuki S, Shiraishi H, Iwasaka T, Izuhara K
  • Organizer: 21st International Congress of Clinical Chemistry and Laboratory Medicine
  • Place of Presentation: ベルリン,ドイツ
  • Year and Date: 2011-05-17
• [Presentation] Development of combined measurement of squamous cell carcinoma antigens 1 and 2 as a potential companion diagnostic for anti-IL-4/IL-13 therapies in allergic diseases (2011)
  • Author(s): Ohta S, Shibata R, Nakao Y, Azuma Y, Taniguchi K, Arima K, Suzuki S, Shiraishi H, Iwasaka T, Izuhara K
  • Organizer: 21st International Congress of Clinical Chemistry and Laboratory Medicine
  • Place of Presentation: ベルリン,ドイツ
  • Year and Date: 2011-05-17
• [Presentation] Distinct signal codes generate dendritic cell functional plasticity. (2010)
  • Author(s): Arima K, Watanabe N, Hanabuchi S, Chang M, Sun S, Liu Y
  • Organizer: 14h International congress of Immunology.
  • Place of Presentation: Kobe (Japan)
  • Year and Date: 2010-08-24
• [Presentation] TSLPとアレルギー(シンポジスト) (2010)
  • Author(s): 有馬和彦
  • Organizer: 第31回日本炎症・再生医学会
  • Place of Presentation: 東京都
  • Year and Date: 2010-08-06
• [Presentation] TSLPとアレルギー (2010)
  • Author(s): 有馬和彦, 出原賢治, Liu Yong-Jun
  • Organizer: 第31回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2010-08-06
• [Book] Thymic stromal lymphopoietin. In : Inflammation and Allergy Drug Design (2011)
  • Author(s): Arima K, Liu Y-J
  • Publisher: Wiley-Blackwell
• [Book] IL-4. In :疾患モデルの作製と利用-免疫疾患 (2011)
  • Author(s): 出原賢治, 有馬和彦, 鈴木章一, 白石裕士, 太田昭一郎
  • Publisher: 株式会社エル・アイ・シー
• [Book] IL-13. In :疾患モデルの作製と利用-免疫疾患 (2011)
  • Author(s): 出原賢治, 有馬和彦, 鈴木章一, 白石裕士, 太田昭一郎
  • Publisher: 株式会社エル・アイ・シー
• [Book] Thymic stromal lymphopoietin. In : Inflammation and Allergy Drug Design (2011)
  • Author(s): Arima K, Liu YJ
  • Publisher: Wiley-Blackwell, London
• [Book] IL-4. In:疾患モデルの作製と利用-免疫疾患 (2011)
  • Author(s): 出原賢治, 有馬和彦, 鈴木章一, 白石裕士, 太田昭一郎
  • Publisher: 株式会社エル・アイ・シー.東京
• [Book] IL-13. In:疾患モデルの作製と利用-免疫疾患 (2011)
  • Author(s): 出原賢治, 有馬和彦, 鈴木章一, 白石裕士, 太田昭一郎
  • Publisher: 株式会社エル・アイ・シー.東京
• [Remarks]
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/index.php
• [Remarks]
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/index.php
• [Remarks]
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/index.php
• [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 (2012)
  • Inventor(s): 出原賢治,有馬和彦,鈴木章一,白石裕士,太田昭一郎
  • Industrial Property Rights Holder: 国立大学法人佐賀大学
  • Filing Date: 2012-01-24
• [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 (2012)
  • Inventor(s): 出原賢治, 有馬和彦, 他
  • Industrial Property Rights Holder: 佐賀大学
  • Industrial Property Number: 2012-011838
  • Filing Date: 2012-01-24
• [Patent(Industrial Property Rights)] 慢性副鼻腔炎の検出方法 (2011)
  • Inventor(s): 出原賢治,太田昭一郎,有馬和彦,白石裕士,鈴木章一,太田伸男,石田晃弘,鈴木祐輔
  • Industrial Property Rights Holder: 出原賢治,太田昭一郎,有馬和彦,白石裕士,鈴木章一,太田伸男,石田晃弘,鈴木祐輔
  • Filing Date: 2011-10-31
• [Patent(Industrial Property Rights)] ペリオスチンの特定領域に結合する抗体、並びにこの抗体を用いるペリオスチンの測定方法、測定試薬及び正確性の改善方法 (2011)
  • Inventor(s): 出原賢治,太田昭一郎,有馬和彦,白石裕士,鈴木章一,星野友昭,東義則,小野純也
  • Industrial Property Rights Holder: 国立大学法人佐賀大学
  • Filing Date: 2011-09-06
• [Patent(Industrial Property Rights)] ペリオスチンの特定領域に結合する抗体、並びにこの抗体を用いるペリオスチンの測定方法、測定試薬及び正確性の改善方法 (2011)
  • Inventor(s): 出原賢治, 有馬和彦, 他
  • Industrial Property Rights Holder: 佐賀大学
  • Industrial Property Number: 2011-194323
  • Filing Date: 2011-09-06
• [Patent(Industrial Property Rights)] 慢性副鼻腔炎の検出方法 (2011)
  • Inventor(s): 出原賢治, 有馬和彦, 他
  • Industrial Property Rights Holder: 佐賀大学
  • Industrial Property Number: 2011-238913
  • Filing Date: 2011-10-31
• [Patent(Industrial Property Rights)] 増殖糖尿病網膜症の検出方法および予防・治療剤のスクリーニング方法 (2010)
  • Inventor(s): 出原賢治, 有馬和彦, 他
  • Industrial Property Rights Holder: 佐賀大学
  • Industrial Property Number: 2010-093240
  • Filing Date: 2010-04-14
• [Patent(Industrial Property Rights)] ペリオスチン測定の正確性の改善方法 (2010)
  • Inventor(s): 出原賢治, 有馬和彦, 他
  • Industrial Property Rights Holder: 佐賀大学
  • Industrial Property Number: 2010-200564
  • Filing Date: 2010-09-08
• [Patent(Industrial Property Rights)] 胆管細胞癌の検出方法および予防・治療剤のスクリーニング方法 (2010)
  • Inventor(s): 出原賢治, 有馬和彦, 他
  • Industrial Property Rights Holder: 佐賀大学
  • Filing Date: 2010-12-02
  • Overseas