Study on Induction of Th2 response and allergic inflammation by basophils

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390145
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Hyogo College of Medicine
• Principal Investigator: NAKANISHI Kenji Hyogo College of Medicine, 医学部, 教授 (60172350)
• Co-Investigator(Kenkyū-buntansha): YOSHIMOTO Tomohiro 兵庫医科大学, 医学部, 教授 (60241171) ; NAKAHIRA Masakiyo 兵庫医科大学, 医学部, 助教 (60454758)
• Project Period (FY): 2008 – 2010
• Keywords: 好塩基球 / Th2細胞 / 抗原提示 / アレルギー性炎症 / アレルゲン / IgE複合体

Research Abstract

Basophils, accounting for less than 1% of total circulating granulocytes, constitutively express FcεR1, and upon crosslinking of FcεR1-bound IgE with multivalent antigens, immediately release various kinds of effector molecules such as histamine and lipid mediators, and Th2-associated cytokines such as IL-4 and IL-13, causing immediate type hypersensitivity. Furthemore, basophils express IL-18R and IL-33R and very strongly produce IL-4 and IL-13 in response to IL-18 and/or IL-33. We have demonstrated that basophils express MHC class II and CD80/86, have the potential to take-up and process protein antigen (Ag), particularly Ag-IgE complexes, and to present peptide with MHC class II and produce IL-4, revealing that basophils are APC, which selectively induce Th2 cells.

Research Products

• [Journal Article] Basophils as APC in Th2 response in allergic inflammation and parasite infection. (2010)
  • Author(s): Nakanishi K
  • Journal Title: Curr Opin Immunol 22 Pages: 814-20
  • Peer Reviewed
• [Journal Article] Basophils are potent antigen-presenting cells that selectively induce Th2 cells. (2010)
  • Author(s): Nakanishi K
  • Journal Title: Eur J Immunol. 40 Pages: 1836-42
  • Peer Reviewed
• [Journal Article] The TLR4/TRIF-Mediated Activation of NLRP3 Inflammasome Underlies Endotoxin-Induced Liver Injury in Mice. (2010)
  • Author(s): Tsutsui H, Imamura M, Fujimoto J, Nakanishi K
  • Journal Title: Gastroenterol Res Pract Pages: 641865
• [Journal Article] Granzyme B is a novel interleukin-18 converting enzyme. (2010)
  • Author(s): Omoto Y, Yamanaka K, Tokime K, Kitano S, Kakeda M, Akeda T, Kurokawa I, Gabazza EC, Tsutsui H, Katayama N, Yamanishi K, Nakanishi K, Mizutani H
  • Journal Title: J Dermatol Sci 59 Pages: 129-35
• [Journal Article] The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. (2010)
  • Author(s): Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K, Matsuyama T, Yui K, Tsujimura T, Standley DM, Nakanishi K, Nakai K, Akira S
  • Journal Title: Nat Immunol 11 Pages: 936-44
  • Peer Reviewed
• [Journal Article] Contribution of IL-18 to eosinophilic airway inflammation induced by immunization and challenge with Staphylococcus aureus proteins. (2010)
  • Author(s): Kuroda-Morimoto M, Tanaka H, Hayashi N, Nakahira M, Imai Y, Imamura M, Yasuda K, Yumikura-Futatsugi S, Matsui K, Nakashima T, Sugimura K, Tsutsui H, Sano H, Nakanishi K
  • Journal Title: Int Immunol 22 Pages: 561-70
  • Peer Reviewed
• [Journal Article] Contribution of IL-33 to induction and augmentation of experimental allergic conjunctivitis. (2010)
  • Author(s): Matsuba-Kitamura S, Yoshimoto T, Yasuda K, Futatsugi-Yumikura S, Taki Y, Muto T, Ikeda T, Mimura O, Nakanishi K
  • Journal Title: Int Immunol 22 Pages: 479-89
  • Peer Reviewed
• [Journal Article] Importance of IL-18-Induced Super Th1 Cells for the Development of Allergic Inflammation. (2010)
  • Author(s): Nakanishi K, Tsutsui H, Yoshimoto T
  • Journal Title: Allergol Int 59 Pages: 137-41
  • Peer Reviewed
• [Journal Article] IFN-γis a master regulator of endotoxin shock syndrome in mice primed with heat-killed Propionibacterium acnes. (2010)
  • Author(s): Kawa K, Tsutsui H, Uchiyama R, Kato J, Matsui K, Iwakura Y, Matsumoto T, Nakanishi K
  • Journal Title: Int Immunol 22 Pages: 157-66
  • Peer Reviewed
• [Journal Article] A functional polymorphism in IL-18 is associated with severity of bronchial asthma. (2009)
  • Author(s): Harada M, Obara K, Hirota T, Yoshimoto T, Hitomi Y, Sakashita M, Doi S, Miyatake A, Fujita K, Enomoto T, Taniguchi M, Higashi N, Fukutomi Y, Nakanishi K, Nakamura Y, Tamari M
  • Journal Title: Am J Respir Crit Care Med 180 Pages: 1048-55
  • Peer Reviewed
• [Journal Article] Basophils contribute to TH2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4^+ T cells. (2009)
  • Author(s): Yoshimoto T, Yasuda K, Tanaka H, Nakahira M, Imai Y, Fujimori Y, Nakanishi K
  • Journal Title: Nat Immunol 10 Pages: 706-12
  • Peer Reviewed
• [Journal Article] Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice. (2009)
  • Author(s): Imamura M, Tsutsui H, Yasuda K, Uchiyama R, Yumikura-Futatsugi S, Mitani K, Hayashi S, Akira S, Taniguchi S, Van Rooijen N, Tschopp J, Yamamoto T, Fujimoto J, Nakanishi K
  • Journal Title: J Hepatol 51 Pages: 333-41
  • Peer Reviewed
• [Journal Article] Association of serum IL-33 level and the IL-33 genetic variant with Japanese cedar pollinosis. (2008)
  • Author(s): Sakishita M., Yoshimoto T., Hirota T., Harada M., Okubo K., Osawa Y., Fujieda S., Nakamura Y., Yasuda K., Nakanishi K., Tamari M.
  • Journal Title: Clin.Exp.Allergy 38 Pages: 1875-1881
  • Peer Reviewed
• [Journal Article] Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system. (2008)
  • Author(s): Kondo Y., Yoshimoto T., Yasuda K., Futatsugi-Yumikura S., Morimoto M., Hayashi N., Hoshino T., Fujimoto J., Nakanishi K.
  • Journal Title: Int.Immunol. 20 Pages: 791-800
  • Peer Reviewed
• [Journal Article] Interferon-γ is a therapeutic target molecule for prevention of postoperative adhesion formation. (2008)
  • Author(s): Kosaka H., Yoshimoto T., Fujimoto J., Nakanishi K.
  • Journal Title: Nat.Med. 14 Pages: 437-441
  • Peer Reviewed
• [Journal Article] Protective effect of IL-18 on kainate-and IL-1β-induced cerebellar ataxia in mice. (2008)
  • Author(s): Andoh T., Kishi H., Motoki K., Nakanishi K., Kuraishi Y., Muraguchi A.
  • Journal Title: J.Immunol. 180 Pages: 2322-2328
  • Peer Reviewed
• [Journal Article] Demonstration of cooperative contribution of MET- and EGFR-mediated STAT3 phosphorylation to liver regeneration by exogenous suppressor of cytokine signalings. (2008)
  • Author(s): Seki E., Kondo Y., Iimuro Y., Naka T., Son G., Kishimoto T., Fujimoto J., Tsutsui H., Nakanishi K.
  • Journal Title: J.Hepatol. 48 Pages: 237-245
• [Presentation] Innate and acquired immunity in expulsion of intestinal nematode. (2010)
  • Author(s): 中西憲司
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 2010-08-27
• [Presentation] Basophils are potentantigen-presenting cells which selectively induce Th2 cells. (2010)
  • Author(s): 中西憲司
  • Organizer: Adaptive and innate immune response to neglected tropical diseases, US-Japan Cooperative Medical Science Program
  • Place of Presentation: San Diego
  • Year and Date: 2010-01-09
• [Presentation] NKT IFN-γ production in response to cancel cauterization induces intestinal adhesion formation by reciprocal regulation of plasminogen activator inhibitor type 1(PAI)and tissue-type plasminogen activator (tPA). (2009)
  • Author(s): 中西憲司
  • Organizer: The 5th International Symposium on CD1/NKT Cells
  • Place of Presentation: Kamakura
  • Year and Date: 2009-03-26
• [Presentation] Basophils induce and augment Th2 response. (2008)
  • Author(s): Nakanishi K., Yoshimoto T.
  • Organizer: 第38回日本免疫学会総会・学術集会(日本免疫学会総会・学術集会記録,38, 2, 2008.)
  • Place of Presentation: 京都(シンポジウム)
  • Year and Date: 20081201-20081203
• [Presentation] 術後の腸管癒着も免疫学的機序を基盤に形成される (2008)
  • Author(s): 中西憲司
  • Organizer: 免疫難病・感染症等の先進医療技術」第5回(最終)公開シンポジウム(要旨集,13-16,2008.)
  • Place of Presentation: 東京(シンポジウム)
  • Year and Date: 2008-12-15
• [Patent(Industrial Property Rights)] Th2細胞誘導用組成物およびTh2型疾患の治療組成物,ならびにこれらの利用 (2009)
  • Inventor(s): 善本知広,中西憲司
  • Industrial Property Number: 特許,PCT/JP2009/005625
  • Filing Date: 2009-10-26
• [Patent(Industrial Property Rights)] 実験動物の腸管癒着を形成する方法、腸管癒着実験動物の製造方法、腸管癒着抑制剤のスクリーニング方法及び腸管癒着抑制剤 (2007)
  • Inventor(s): 善本知広、中西憲司、藤元治朗
  • Industrial Property Rights Holder: 科学技術振興機構
  • Industrial Property Number: 特許,特願2007-033904
  • Filing Date: 2007-02-14