Elucidation and Application of Tissue-specific Regulatory System in Mast Cells

• Project/Area Number: 26893047
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: Kurashima Yosuke 東京大学, 医科学研究所, 助教 (30729372)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: マスト細胞 / 皮膚科学 / 接触性皮膚炎 / 線維芽細胞 / 受容体 / 皮膚炎 / 炎症 / アレルギー / 皮膚疾患 / 好中球 / ゲノム編集法

Outline of Final Research Achievements

Mast cells are known as effector cells in various allergic diseases and have been classified into connective tissue type (e.g. skin, blood vessel, and peritoneal cavity) and mucosal tissue type (e.g. lung and intestinal mucosa).
In this research, we have found tissue specific gene expression patterns in mast cells and a surface molecule bearing inhibitory motif was strongly expressed in the skin mast cells but not in mast cells located in the other tissues.
Mice lacking this molecule were sensitive to skin inflammations compared to wild type mice. These findings suggested that regulation of this molecule would be novel strategies for the suppression of skin inflammation.

Research Products

• [Journal Article] Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut (2015)
  • Author(s): J. Kunisawa, M. Arita, T. Hayasaka, T. Harada, R. Iwamoto, R. Nagasawa, S. Shikata, T. Nagatake, H. Suzuki, E. Hashimoto, Y. Kurashima, Y. Suzuki, H. Arai, M. Setou, and H. Kiyono
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 9750-9750
  • DOI: 10.1038/srep09750
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The gut microbiota and inflammatory bowel disease (2015)
  • Author(s): 後藤義幸、倉島洋介、清野宏
  • Journal Title: Current Opinion Rheumatology Volume: 27 Issue: 4 Pages: 388-396
  • DOI: 10.1097/bor.0000000000000192
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pathophysiological role of extracellular purinergic mediators in the control of intestinal inflammation. (2015)
  • Author(s): Kurashima Y, Kiyono H, Kunisawa J.
  • Journal Title: Mediators Inflamm. Volume: 427125 Issue: 1 Pages: 427125-427125
  • DOI: 10.1155/2015/427125
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Negative regulation of DSS-induced experimental colitis by PILRα. (2015)
  • Author(s): Kishida, K., Kohyama, M., Kurashima, Y., Kogure, Y., Wang, J., Hirayasu, K., Suenaga, T., Kiyono, H., Kunisawa, J. and Arase, H.
  • Journal Title: Int. Immunol. Volume: - Issue: 6 Pages: 307-314
  • DOI: 10.1093/intimm/dxv004
  • Peer Reviewed / Open Access
• [Journal Article] The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells. (2015)
  • Author(s): Tsai, S-H., Kinoshita, M., Kusu, T., Kayama, H., Okumura, R., Ikeda, K., Shimada, Y., Takeda, A., Yoshikawa, S., Obata-Ninomiya, K., Kurashima, Y., Sato, S., Umemoto, E., Kiyono, H., Karasuyama, H. and Takeda, K.
  • Journal Title: Immunity Volume: 42(2) Issue: 2 Pages: 279-293
  • DOI: 10.1016/j.immuni.2015.01.015
  • Peer Reviewed / Open Access
• [Journal Article] Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicostetraenoic acid in the gut (2015)
  • Author(s): J. Kunisawa, M. Arita, T. Hayasaka, T. Harada, R. Iwamoto, R. Nagasawa, S. Shikata, T. Nagatake, H. Suzuki, E. Hashimoto, Y. Kurashima, Y. Suzuki, H. Arai, M. Setou, and H. Kiyono
  • Journal Title: Scientific Report Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Negative regulation of DSS-induced experimental colitis by PILRα (2015)
  • Author(s): Kishida K, Kohyama M, Kurashima Y, Kogure Y, Wang J, Hirayasu K, Suenaga T, Kiyono H, Kunisawa J, Arase H
  • Journal Title: Int Immunol. Volume: -
  • Peer Reviewed
• [Journal Article] The enzyme cyp26b1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis. (2014)
  • Author(s): Kurashima Y, Amiya T, Fjisawa K, Shibata N, Suzuki Y, Kogure Y, Hashimoto E, Otsuka A, Kabashima K, Sato S, Sato T, Kubo M, Akira S, Miyake K, Kunisawa J, Kiyono H.
  • Journal Title: Immunity Volume: 40 Issue: 4 Pages: 530-541
  • DOI: 10.1016/j.immuni.2014.01.014
  • Peer Reviewed / Open Access
• [Journal Article] Pathophysiological role of extracellular purinergic mediators in the control of intestinal inflammation (2014)
  • Author(s): Y. Kurashima, H. Kiyono, and J. Kunisawa
  • Journal Title: Mediators of Inflammation Volume: Article ID 427125 Pages: 1-9
  • Peer Reviewed / Open Access
• [Journal Article] Peyer’s patches and mesenteric lymph nodes cooperatively promote enteropathy in a mouse model of food allergy． (2014)
  • Author(s): Haruyo Nakajima-Adachi, Akira Kikuchi, Yoko Fujimura, Kyoko Shibahara, Tsuyoshi Makino, Masae Goseki-Sone, Miran Kihara-Fujioka, Tomonori Nochi, Yosuke Kurashima, Osamu Igarashi, Masafumi Yamamoto, Jun Kunisawa, Masako Toda, Shuichi Kaminogawa, Ryuichiro Sato, Hiroshi Kiyono, Satoshi Hachimura
  • Journal Title: ＰＬｏＳ Ｏｎｅ Volume: 9 Issue: 10 Pages: e107492-e107492
  • DOI: 10.1371/journal.pone.0107492
  • Peer Reviewed / Open Access
• [Journal Article] New era for mucosal mast cells : their roles in inflammation, allergic immune rasposes and adjuvant development. (2014)
  • Author(s): Kurashima Y, Kiyono H.
  • Journal Title: Exp Mol Med. Volume: 46 Issue: 3 Pages: e83-e83
  • DOI: 10.1038/emm.2014.7
  • Peer Reviewed / Open Access
• [Presentation] 疾患特異的マスト細胞活性化機序の解明をその制御 (2016)
  • Author(s): 倉島洋介
  • Organizer: 第136薬学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-28
• [Presentation] Elucidation and Regulation of Disease-specific Mast Cell Activations (2015)
  • Author(s): Yosuke Kurashima
  • Organizer: Mini-symposium for Mucosal Immunology and Allergy therapeutics
  • Place of Presentation: 千葉
  • Year and Date: 2015-12-16
  • Invited
• [Presentation] レチノイン酸代謝による皮膚マスト細胞の鎮静化 (2015)
  • Author(s): 倉島洋介
  • 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
  • Invited
• [Presentation] Analysis of a mast cell-suppressive milieu on the body surface for the prevention and treatment of inflammatory diseases (2015)
  • Author(s): Yosuke Kurashima
  • Organizer: The American Association of Immunologists Immunology 2015
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2015-05-08
  • Int'l Joint Research / Invited
• [Presentation] Gut Microflora Influences Pathology in the Kawasaki Disease (KD) VasculitisMouse Model (2015)
  • Author(s): D. Wakita, Y. Kurashima, Y. Takasato, Y. Lee, K. Shimada, S. Chen, T. R. Crother, M. C. Fishbein, T.J.A. Lehman, H. Kiyono, and M. Arditi
  • Organizer: International Kawasaki Disease Symposium
  • Place of Presentation: ハワイ、アメリカ
  • Year and Date: 2015-02-03 – 2015-02-06
• [Presentation] MD-1 affects BCR-S1P1 association (2014)
  • Author(s): S. Akashi-Takamura, N. Yamakawa, T. Shibata, Y. Kurashima, J. Kunisawa, H. Kiyono, K. Suzuki, .J Kikuta, M. Ishii, K. Miyake
  • 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] Critical role of TSLP-TSLPR interaction in inducing secretory IgA responses after mucosal immunizations (2014)
  • Author(s): S. Joo, Y. Fukuyama, Y. Kurashima, S. F. Ziegler, Y. Yuki, E.J. PARK, H. Kiyono
  • 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] Resistance to a helminthic infection is dependent on mast cell activation mediated by ATP in Spi-B-deficient mice (2014)
  • Author(s): C. Shimokawa, T. Kanaya, K. Ishiwata, Y. Kurashima, H. Kiyono, T. Kaisho, H. Ohno
  • 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] Tissue-specific signals control mast cell function for the maintenance of tissue homeostasis (2014)
  • Author(s): Y. Kurashima
  • Organizer: the 1st International Symposium on Mucosal Immunity and Vaccine Development 2014
  • Place of Presentation: 東京
  • Year and Date: 2014-10-21
  • Invited
• [Presentation] Tissue-specific signals control mast cell function for the maintenance of tissue homeostasis (2014)
  • Author(s): Y. Kurashima
  • Organizer: 2nd Innocation Summit Chronic Inflammation and Autoimmune Diseases
  • Place of Presentation: 東京
  • Year and Date: 2014-10-02
  • Invited
• [Book] Clinical Immunology & Allergology (2015)
  • Author(s): Sato, T., Kurashima, Y., Kunisawa, J. and Kiyono, H.
  • Total Pages: 7
  • Publisher: KAGAKU-HYORONSHA CO. Ltd.
• [Book] Clinical Immunology & Allergy (2015)
  • Author(s): Kurashima, Y., Kogure, Y., Fukui, W., and Kiyono, H.
  • Total Pages: 7
  • Publisher: KAGAKU-HYORONSHA CO. Ltd.
• [Book] Infection, Inflammation, Immunity (2015)
  • Author(s): Kurashima, Y., Sato, T., Kiyono, H.,
  • Total Pages: 12
  • Publisher: TORII PHARMACEUTICAL CO., LTD
• [Book] Journal of Clinical and Experimental Medicine (2015)
  • Author(s): Kurashima, Y., Takasato, Y., Konuma, Y., and Kiyono. H.
  • Total Pages: 6
  • Publisher: ISHIYAKU PUB
• [Book] Inflammation and Immunity (2015)
  • Author(s): Kurashima, Y., and Kiyono, H
  • Total Pages: 7
  • Publisher: SENTAN IGAKY KAGAKU SHA
• [Book] Clinical Immunology & Allergy (2015)
  • Author(s): Takasato, T., Kurashima, Y. and Kiyono H.
  • Total Pages: 7
  • Publisher: KAGAKU-HYORONSHA CO. Ltd.
• [Book] 感染・炎症・免疫 (2015)
  • Author(s): 倉島洋介、佐藤健、清野宏
  • Publisher: 羊土社
• [Book] 臨床免疫・アレルギー科 (2015)
  • Author(s): 佐藤健、倉島洋介、國澤純、清野宏
  • Total Pages: 7
  • Publisher: 科学評論社
• [Book] 生化学 (2014)
  • Author(s): 倉島洋介、清野宏、國澤純
  • Total Pages: 5
  • Publisher: 日本生化学会
• [Book] Bioindustry (2014)
  • Author(s): 高里良宏、倉島洋介、清野宏、國澤純
  • Total Pages: 6
  • Publisher: CMC Publishing CO., LTD