Study on a novel mechanism by which IgE/FcεRI mediates chronic allergic inflammation

• Project/Area Number: 16616004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: アレルギー
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KARASUYAMA Hajime Tokyo Medical and Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (60195013)
• Co-Investigator(Kenkyū-buntansha): MINEGISHI Yoshiyuki Tokyo Medical and Dental University, Associate Professor, 大学院・医歯学総合研究科, 助教授 (10343154) ; NISHIKAWA Kiyoshi Tokyo Medical and Dental University, Emeritus Professor, 名誉教授 (20077647)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,800,000 (Direct Cost: ¥3,800,000); Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: chronic allergy / atopic dermatitis / model mice / IgE / T cell / mast cell / basophil / eosinophil / 抗体

Research Abstract

The recruitment of basophils into the sites of allergic inflammation is often observed. However, no definitive evidence has been provided that basophils are crucially involved in the pathogenesis of chronic allergic disorders. Basophils represent less than 1% of peripheral blood leukocytes. and have often been considered as minor and possibly redundant "circulating mast cells". In this study, we have demonstrated that basophils play an important and non-redundant role and are responsible for the development of IgE-mediated chronic allergic inflammation, independently of T cells and mast cells. A single subcutaneous injection of multivalent antigens elicited not only immediate- and late-phase ear swelling but also delayed-onset ear swelling with massive eosinophil infiltration in mice sensitized with antigen-specific IgE and IgE transgenic mice. Mast cells were essential for the immediate- and late-phase ear swelling but dispensable for the delayed one. T cells were also dispensable for the latter. The delayed-onset allergic inflammation was not developed in FcεRI-deficient mice, but it was restored in these mice by transferring FcεRI-expressing basophils from normal mice. These findings indicate a novel mechanism of development of chronic allergic inflammation that is induced by basophils through the-interaction of antigen, IgE, and FcεRI. The present study implies that basophils and their products could be good targets to treat this type of chronic allergic inflammation.

Research Products

• [Journal Article] Different stabilities of the structurally related receptors for IgE and IgG on the cell surface are determined by length of the stalk region in their α-chains. (2006)
  • Author(s): Kubota, T., Mukai, K., Minegishi, Y., Karasuyama, H.
  • Journal Title: The Journal of Immunology 176 Pages: 7008-7014
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Different stabilities of the structurally related receptors for IgE and IgG on the cell surface are determined by length of the stalk region in their α-chains. (2006)
  • Author(s): Kubota, T., Mukai, K., Minegishi, Y., Karasuyama H.
  • Journal Title: The Journal of Immunology 176 Pages: 7008-7014
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ovalbumin-specific IgE modulates ovalbumin-specific T-cell response after repetitive oral antigen administration. (2005)
  • Author(s): Omata, N., Ohshima, Y., Yasutomi, M., Yamada, A., Karasuyama, H., Mayumi, M.
  • Journal Title: The Journal of Allergy and Clinical Immunology 115 Pages: 822-827
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling. (2005)
  • Author(s): Shinohara, H., Inoue, A., Toyama-Sorimachi, N., Nagai, Y., Yasuda, T., Suzuki, H., Horai, R., Iwakura, Y., Yamamoto, T., Karasuyama, H., Miyake, K., Yamanashi, Y.
  • Journal Title: The Journal of Experimental Medicine 201 Pages: 333-339
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependent manner. (2005)
  • Author(s): Toyama-Sorimachi, N., Omatsu, Y., Onoda, A., Tsujimura, Y., Iyoda, T., Kikuchi-Maki, A., Sorimachi, H., Dohi, T., Taki, S., Inaba, K., Karasuyama, H.
  • Journal Title: The Journal of Immunology 74 Pages: 4621-4629
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Activation of NFκ-B promotes the transition of large, CD43^+ pre-B cells to small, CD43^- pre-B cells. (2005)
  • Author(s): Jimi, E., Phillips, R.J., Rincon, M., Voll, R., Karasuyama, H., Flavell, R., Ghosh, S.
  • Journal Title: International Immunology 17 Pages: 815-825
  • NAID: 10019358989
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Selection of stereotyped VH81X-μH chains via preB cell receptor early in ontogeny and their conservation in adults by marginal zone B cells. (2005)
  • Author(s): Kawano, Y., Yoshikawa, S., Minegishi, Y., Karasuyama, H.
  • Journal Title: International Immunology 17 Pages: 857-867
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. (2005)
  • Author(s): Mukai, K., Matsuoka, K., Taya, C., Suzuki, H., Yokozeki, H., Nishioka, K., Hirokawa, K., Etori, M., Yamashita, M., Kubota, T., Minegishi, Y., Yonekawa, H., Karasuyama, H.
  • Journal Title: Immunity 23 Pages: 191-202
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 好塩基球が主役を演じる慢性アレルギー炎症誘発機構 (2005)
  • Author(s): 向井香織, 烏山 一
  • Journal Title: アレルギー科 20(2) Pages: 179-185
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling. (2005)
  • Author(s): Shinohara, H, Inoue, A, Toyama-Sorimachi, N, Nagai Y, Yasuda T, Suzuki H, Horai R, Iwakura Y, Yamamoto T, Karasuyama H, Miyake K, Yamanashi Y.
  • Journal Title: The Journal of Experimental Medicine 201 Pages: 333-339
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling. (2005)
  • Author(s): Shinohara H, Inoue A, Toyama-Sorimachi N, Nagai Y, Yasuda T, Suzuki I, Horai R, Iwakura Y, Yamamoto T, Karasuyama H, Miyake K Yamanashi Y.
  • Journal Title: The Journal of Experimental Medicine 201 Pages: 333-339
• [Journal Article] Ovalbumin-specific IgE modulates ovalbumin-specific T-cell response after repetitive oral antigen administration. (2005)
  • Author(s): Omata N, Ohshima Y, Yasutomi M, Yamada A, Karasuyama H, Mayumi M.
  • Journal Title: The Journal of Allergy and Clinical Immunology 115 Pages: 822-827
• [Journal Article] Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependent manner. (2005)
  • Author(s): Toyama-Sorimachi, N., Omatsu, Y., Onoda, A., Tsujimura, Y., Iyoda, T, Kikuchi-Maki, A., Sorimachi, H, Dohi T., Taki, S., Inada, K., Karasuyama, H.
  • Journal Title: Time Journal of Immunology 74 Pages: 4621-4629
• [Journal Article] Activation of NFκ-B promotes the transition of large, CD43^+ pre-B cells to small, CD43^- pre-B cells. (2005)
  • Author(s): Jimi, E., Phillips, R.J., Rincon, M., Voll R., Karasuyama, H., Flavell, R., Ghosh, S.
  • Journal Title: International Immunology 17 Pages: 815-825
  • NAID: 10019358989
• [Journal Article] Selection of stereotyped VH81X- μ H chains via preB cell receptor early in ontogeny and their conservation in adults by marginal zone B cells. (2005)
  • Author(s): Kawano, Y., Yoshikawa, S., Minegishi Y., Karasuyama, H.
  • Journal Title: International Immunology 17 Pages: 857-867
• [Journal Article] Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. (2005)
  • Author(s): Mukai, K., Matsuoka, K., Taya, C., Suzuki, H., Yokozeki, H., Nishioka, K., Hirokawa, K., Etori M., Yamashita, M., Kubota, T., Minegishi, Y., Yonekawa H., Karasuyama, H.
  • Journal Title: Immunity 23 Pages: 191-202
• [Journal Article] Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling. (2005)
  • Author(s): Shinohara H, Inoue A, Toyama-Sorimachi N, Nagai Y, Yasuda T, Suzuki H, Horai R, Iwakura Y, Yamamoto T, Karasuyama H, Miyake K, Yamanashi Y
  • Journal Title: Journal of experimental medicine 201 Pages: 333-339
• [Journal Article] IgE-dependent enhancement of Th2 cell-mediated allergic inflammation in the airways. (2004)
  • Author(s): Maezawa, Y., Nakajima, H., Seto, Y., Suto, A., Kumano, K., Kubo, S., Karasuyama, H., Saito, Y., Iwamoto, I.
  • Journal Title: Clinical and Experimental Immunology 135 Pages: 12-18
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Deficiency of BLNK hampers PLC-γ2 phosphorylation and Ca2+ influx induced by the pre-B cell receptor in human pre-B cells. (2004)
  • Author(s): Taguchi, T., Kiyokawa, N., Takenouchi, H., Matsui, J., Tang, W., Nakajima, H., Suzuki, K., Shiozawa, Y., Saito, M., Katagiri, Y.U., Takahashi, T., Karasuyama, H., Matsuo, Y., Okita, H., Fujimoto, J.
  • Journal Title: Immunology 112 Pages: 575-582
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Diagnostic importance of CD179a/b as markers of precursor B-cell lymphoblastic lymphoma. (2004)
  • Author(s): Kiyokawa, N., Sekino, T., Matsui, T., Takenouchi, H., Mimori, K., Tang, W.R., Matsui, J., Taguchi, T., Katagiri, Y.U., Okita, H., Matsuo, Y., Karasuyama, H., Fujimoto, J.
  • Journal Title: Modern Pathology 17 Pages: 423-429
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ly49Q, a member of Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture. (2004)
  • Author(s): Toyama-Sorimachi, N., Tsujimura, Y., Maruya, M., Onoda, A., Kubota, T., Koyasu, S., Inaba, K., Karasuyama, H.
  • Journal Title: Proceedings of the National Academy of Sciences of the USA 101 Pages: 1016-1021
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 遺伝子改変モデル動物で誘導される新たな慢性アレルギー炎症反応に対するシクロスポリンの作用 (2004)
  • Author(s): 烏山 一
  • Journal Title: 医薬ジャーナル 40 Pages: 183-187
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] IgE受容体研究の最近の進歩 (2004)
  • Author(s): 烏山 一
  • Journal Title: Animus 34 Pages: 22-25
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] IgE/FcεRIを介する新たな慢性アレルギー炎症誘発機構 (2004)
  • Author(s): 向井香織, 松岡邦枝, 烏山 一
  • Journal Title: 臨床免疫 41(2) Pages: 195-199
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Diagnostic importance of CD 179a/b as markers of precursor B-cell lymphoblastic lymphoma. (2004)
  • Author(s): Kiyokawa, N., Sekino, T., Matsui, T., Takenouchi, H., Mimori, K., Tang, W.R., Matsui, J., Taguchi, T., Katagiri, Y.U., Okita, H., Matsuo, Y., Karasuyama, H., Fujimoto, J.
  • Journal Title: Modern Pathology 17 Pages: 423-429
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] IgE-dependent enhancement of Th2 cell-mediated allergic inflammation in the airways. (2004)
  • Author(s): Maezawa Y, Nakajima H, Seto Y, Suto A, Kumano K, Kubo S, Karasuyama H, Saito Y, Iwamoto I.
  • Journal Title: Clinical and experimental Immunology 135 Pages: 12-18
• [Journal Article] Deficiency of BLNK hampers PLC-gamma2 phosphorylation and Ca2+ influx induced by the pre-B-cell receptor in human pre-B cells. (2004)
  • Author(s): Taguchi T, Kiyokawa N, Takenouch H, Matsui J, Tang WR, Nakajima H, Suzuki K, Shiozawa Y, Saito M, Katagiri YU, Takahashi T, Karasuyama H, Matsuo Y, Okita H, Fujimoto J.
  • Journal Title: Immunology 112(4) Pages: 575-582
• [Journal Article] Diagnostic importance of CD179a/b as markers of precursor B-cell lymphoblastic lymphoma. (2004)
  • Author(s): Kiyokawa N, Sekino T, Matsui T, Takenouchi H, Mimori K, Tang WR, Matsui J, Taguchi T, Katagiri YU, Okita H, Matsuo Y, Karasuyame H, Fujimoto J
  • Journal Title: Modern Pathology 17 Pages: 423-423
• [Journal Article] Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture (2004)
  • Author(s): Toyama-Sorimachi N, Tsujimura Y, Maruya M, Onoda A, Kubota T, Koyasu S, Inaba K, Karasuyama H.
  • Journal Title: Proceedings of the national academy of sciences of the United States of America 101 Pages: 1016-1021
• [Journal Article] IgE/FcεRIを介する新たな慢性アレルギー炎症誘発機構 (2004)
  • Author(s): 向井香織, 松岡邦枝, 烏山一
  • Journal Title: 臨床免疫 41(2) Pages: 195-199
• [Book] 生涯教育シリーズ67 日本医師会雑誌特別号 分りやすい免疫疾患 (2005)
  • Author(s): 烏山 一
  • Total Pages: 4
  • Publisher: 日本医師会
  • Description: 「研究成果報告書概要(和文)」より
• [Book] キーワードで理解する免疫学イラストマップ (2004)
  • Author(s): 烏山 一(編集)
  • Publisher: 羊土社