Pathogenic mechanisms of atopic dermatitis

• Project/Area Number: 25253071
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kawakami Toshiaki 国立研究開発法人理化学研究所, 統合生命医科学研究センター, チームリーダー (60143418)
• Co-Investigator(Kenkyū-buntansha): Izuhara Kenji 佐賀大学, 医学部, 教授 (00270463) ; Matsumoto Kenji 国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, 部長 (60181765)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000); Fiscal Year 2015: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000); Fiscal Year 2014: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000); Fiscal Year 2013: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
• Keywords: アトピー性皮膚炎 / マスト細胞 / Phospholipase C-β3 / Stat5 / Periostin / TSLP

Outline of Final Research Achievements

Atopic dermatitis (AD) is a chronic inflammatory skin disease featured with itching and type 2 inflammation. Evidence has been accumulated showing that skin barrier impairment and immune dysregulation underlie the disease. This research project has been focused on revealing the disease pathogenesis at the cellular and molecular levels by studying murine AD models that develop skin inflammation in either a spontaneous or allergen-induced manner. So far, our data have shown that mast cells, but not basophils, are required for allergen-induced skin inflammation. Our analysis of conditional knockout mice lacking the Plcb3 gene encoding phospholipase C-β3 in various cell-specific fashions has not been completed yet. However, our data indicate that Plcb3 in CD4 T cells is not required for spontaneous development of AD-like skin inflammation in Plcb3-decifient mice.

Research Products

• [Journal Article] Hypothetical atopic dermatitis-myeloproliferative neoplasm syndrome. (2015)
  • Author(s): Kawakami, T., Ando, T., and Kawakami, Y.
  • Journal Title: Front. Immunol. Volume: 6 Pages: 434-434
  • DOI: 10.3389/fimmu.2015.00434
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation. (2015)
  • Author(s): Carroll-Portillo, A., Cannon, J.L., te Riet, J., Holmes, A., Kawakami, Y., Kawakami, T., Cambi, A., and Lidke, D.S.
  • Journal Title: J. Cell Biol. Volume: 210 Issue: 5 Pages: 851-864
  • DOI: 10.1083/jcb.201412074
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Signal transduction and chemotaxis in mast cells. (2015)
  • Author(s): Draber, P., Halova, I., Polakovicova, I., and Kawakami, T.
  • Journal Title: Eur. J. Pharmacol. Volume: 778 Pages: 11-23
  • DOI: 10.1016/j.ejphar.2015.02.057
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Suplatast tosilate for treating cutaneous mastocytosis (2015)
  • Author(s): Yasudo, H., Ando, T., Hiwatari, M., and Oka, A.
  • Journal Title: Pediatric Dermatology Volume: 32 Issue: 3
  • DOI: 10.1111/pde.12552
  • Peer Reviewed
• [Journal Article] Signal transduction and chemotaxis in mast cells (2015)
  • Author(s): Draber, P., Halova, I., Polakovicova, I., and Kawakami, T.
  • Journal Title: European Journal of Pharmacology Volume: in press
  • Peer Reviewed
• [Journal Article] アレルギー疾患におけるヒスタミン遊離因子の関与 (2015)
  • Author(s): 柏倉淳一, 安藤智暁, 川上敏明
  • Journal Title: 臨床免疫・アレルギー科 Volume: 63 Pages: 84-88
  • NAID: 40020330518
• [Journal Article] アトピー性皮膚炎におけるマスト細胞のStat5活性化経路の関与 (2015)
  • Author(s): 安藤智暁，川上敏明
  • Journal Title: 臨床免疫・アレルギー科 Volume: in press
  • NAID: 40020505178
• [Journal Article] Signal-transducing adaptor protein-2 controls the IgE-mediated, mast cell-mediated anaphylactic responses. (2014)
  • Author(s): Sekine Y, Nishida K, Yamasaki S, Muromoto R, Kon S, Kashiwakura J, Saitoh K, Togi S, Yoshimura A, Oritani K, Matsuda T
  • Journal Title: J Immunol Volume: 192 Issue: 8 Pages: 3488-3495
  • DOI: 10.4049/jimmunol.1300886
  • Peer Reviewed
• [Journal Article] Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria (2014)
  • Author(s): Fujisawa, D., Kashiwakura, J., Kita, H., Kikukawa, Y., Fujitani, Y., Sasaki-Sakamoto, Y., Kuroda, K., Nunomura, S., Hayama, K., Terui, T., Ra, C., and Okayama, Y.
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 134 Issue: 3 Pages: 622-633
  • DOI: 10.1016/j.jaci.2014.05.004
  • Peer Reviewed
• [Journal Article] Systemic lupus erythematosus complicated with liver cirrhosis in a patient with Papillon-Lefevre syndrome (2014)
  • Author(s): Yasudo, H., Ando, T., Takeuchi, M., Nakano, H., Itonaga, T., Takehara, H., Isojima, T., Miura, K., Harita, Y., Takita, J., and Oka, A.
  • Journal Title: Lupus Volume: 23 Issue: 14 Pages: 1523-1527
  • DOI: 10.1177/0961203314547794
  • Peer Reviewed / Open Access
• [Journal Article] Histamine-releasing factor and immunoglobulins in asthma and allergy (2014)
  • Author(s): Kawakami, T., Kashiwakura, J., and Kawakami, Y.
  • Journal Title: Allergy, Asthma & Immunology Research Volume: 6 Issue: 1 Pages: 6-12
  • DOI: 10.4168/aair.2014.6.1.6
  • Peer Reviewed / Open Access
• [Journal Article] アレルギー炎症とIgE Heterogeneityヒスタミン遊離因子によるマスト細胞活性化調節 (2014)
  • Author(s): 柏倉淳一, 安藤智暁, 川上敏明
  • Journal Title: 化学と生物 Volume: 52 Pages: 496-498
  • NAID: 130005090119
• [Journal Article] Immune regulation by phospholipase C-βisoforms. (2013)
  • Author(s): Xiao, W., Kawakami, Y., and Kawakami, T.
  • Journal Title: Immunol. Res. Volume: 56 Issue: 1 Pages: 9-19
  • DOI: 10.1007/s12026-012-8341-3
  • Peer Reviewed
• [Journal Article] Mast cells are required for full expression of allergen/SEB-induced skin inflammation. (2013)
  • Author(s): Ando, T., Matsumoto, K., Namiranian, S., Yamashita, H., Glatthorn, H., Kimura, M., Dolan, B. R., Lee, J.J., Galli, S.J., Kawakami, Y., Jamora, C., and Kawakami, T.
  • Journal Title: J. Invest. Dermatol. Volume: 133 Issue: 12 Pages: 2695-2705
  • DOI: 10.1038/jid.2013.250
  • Peer Reviewed
• [Journal Article] Salmonella’s masterful skill in mast cell suppression. (2013)
  • Author(s): Kawakami, T. and Ando, T.
  • Journal Title: Immunity Volume: 39 Issue: 6 Pages: 996-998
  • DOI: 10.1016/j.immuni.2013.11.007
  • Peer Reviewed
• [Journal Article] Critical role for mast-cell Stat5 activity in skin inflammation. (2013)
  • Author(s): Ando, T., Xiao, W., Gao, P., Namiranian, S., Matsumoto, K., Tomimori, Y., Hong, H., Yamashita, H., Kimura, M., Kashiwakura, J., Hata, T.R., Izuhara, K., Gurish, M.F., Roers, A., Rafaels, N.M., Barnes, K.C., Jamora, C., Kawakami, Y., and Kawakami, T.
  • Journal Title: Cell Reports Volume: 6 Issue: 2 Pages: 366-376
  • DOI: 10.1016/j.celrep.2013.12.029
  • Peer Reviewed / Open Access
• [Presentation] Histamine-releasing factor in food allergy. (2015)
  • Author(s): Kawakami, T.
  • Organizer: The 7th EMBRN International Mast Cell and Basophil Meeting
  • Place of Presentation: Marseille, France
  • Year and Date: 2015-10-21
  • Int'l Joint Research / Invited
• [Presentation] Phospholipase C-β3 in the defense against skin inflammation. (2015)
  • Author(s): Kawakami, T.
  • Organizer: SPC-NUS Workshop “Mast cells in immune disorders and tissue homeostasis
  • Place of Presentation: Paris, France.
  • Year and Date: 2015-10-19
  • Int'l Joint Research / Invited
• [Presentation] Mast cells and the Stat5 activation pathway are required for allergen-induced and spontaneous skin inflammation (2014)
  • Author(s): Tomoaki Ando, Jun-ichi Kashiwakura, Yuko Kawakami, Toshiaki Kawakami
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館、京都市
  • Year and Date: 2014-12-11
• [Presentation] Critical role for mast-cell Stat5 activity in atopic dermatitis (2014)
  • Author(s): Kawakami, T.
  • Organizer: Academy of Immunology and Microbiology (AIM) Workshop on Immunology 2014
  • Place of Presentation: Pohang, Republic of Korea
  • Year and Date: 2014-11-09 – 2014-11-10
  • Invited
• [Presentation] Atopic dermatitis and hematopoietic malignancy: Lessons from studies on (2014)
  • Author(s): Kawakami, T.
  • Organizer: The 14th Annual Meeting of The Korean Atopic
  • Place of Presentation: Seoul, Republic of Korea
  • Year and Date: 2014-11-08
  • Invited
• [Presentation] Critical role for mast-cell Stat5 activity in atopic dermatitis (2014)
  • Author(s): Kawakami, T.
  • Organizer: The LJI-USC Immunology Retreat
  • Place of Presentation: La Jolla, California, USA
  • Year and Date: 2014-04-22
  • Invited
• [Presentation] Phospholipase C-β3 as a tumor suppressor and a guardian of the immune system
  • Author(s): Toshiaki Kawakami
  • Organizer: Special International Symposium “Inositide-Dependent Phospholipase C Activity and Signalling”
  • Place of Presentation: Ulsan, South Korea
  • Invited
• [Presentation] Stat5 regulation: a crucial mediator in mast cell-dependent skin inflammation
  • Author(s): Toshiaki Kawakami
  • Organizer: The 7th International Leukocyte Signal Transduction Conference
  • Place of Presentation: Kos, Greece
  • Invited
• [Presentation] Phospholipase C-β3 as a tumor suppressor and a guardian of the immune system
  • Author(s): Toshiaki Kawakami
  • Organizer: The 5th LIAI-IMS Workshop
  • Place of Presentation: Yokohama, Japan
  • Invited
• [Presentation] Phospholipase C-β3 as a tumor suppressor and a guardian of the immune system
  • Author(s): Toshiaki Kawakami
  • Organizer: 2013 International Conference “Inflammation,Cancer and Metabolic Disorders”
  • Place of Presentation: Zhunan, Miaoli, Taiwan
  • Invited
• [Presentation] Breakfast Seminar entitled “New insights into IgE biology”
  • Author(s): Toshiaki Kawakami
  • Organizer: The Annual Meeting of American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Diego, California, USA
  • Invited
• [Book] A Mouse Model of Atopic Dermatitis. In Mast Cells: Methods and Protocols,Methods in Molecular Biology vol. 1220, (eds. Michael R. Hughes and Kelly M. McNagny) (2015)
  • Author(s): Kawakami, Y. and Kawakami, T
  • Total Pages: 540
  • Publisher: Springer Science+Business Media
• [Book] Basic Techniques to Study FcεRI Signaling in Mast Cells. In Mast Cells: Methods and Protocols, Methods in Molecular Biology vol. 1220, (eds. Michael R. Hughes and Kelly M. McNagny) (2014)
  • Author(s): Kawakami, Y. and Kawakami, T.
  • Total Pages: 540
  • Publisher: Springer Science+Business Media