A role of Plant homeodomain finger protein 11 in class switch recombination to IgE in murine activated B cells

• Project/Area Number: 24591460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Chiba University
• Principal Investigator: ARIMA Masafumi 千葉大学, 医学(系)研究科(研究院), 講師 (00202763)
• Co-Investigator(Kenkyū-buntansha): TOKUHISA Takeshi 千葉大学, 学長 (20134364)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ＰＨＦ１１ / ＩｇＥ / アレルギー / 転写因子 / PHF11 / クラススイッチ / IgE / Allergy

Outline of Final Research Achievements

Polymorphisms of the Plant homeodomain finger protein 11 (PHF11) are strongly associated with high serum IgE levels of atopic patients. We generated Phf11 transgenic (Lckd-Phf11-Tg) mice that express the exogenous murine Phf11 under the control of distal Lck promoter. The exogenous Phf11 promoted CSR to IgG1 and IgE in activated B cells with an increase in germ line transcript (GLT) ε expression. The exogenous Phf11 augmented transcriptional activity of the GLT ε promoters through permissive histone modifications and binding of NF-κB and STAT6. Furthermore, the exogenous Phf11 bound to the GLT ε promoter with increased binding of NF-κB. In an allergic rhinitis model, theTg mice showed a significant increase in the production of OVA-specific IgE and the frequency of nose scratching. Phf11 accelerates CSR to IgE in activated B cells by increasing the transcriptional activity of GLT ε promoter and contributes to the exacerbation of allergic responses.

Research Products

• [Journal Article] Improved sensitivity to venom specific-immunoglobulin E by spiking with the allergen component in Japanese patients suspected of Hymenoptera venom allergy (2015)
  • Author(s): Yoshida, N., Hirata, H., Watanabe, M., Sugiyama, K., Arima, M., Fukushima, Y., Ishii, Y.
  • Journal Title: Allergology International Volume: 64 Issue: 3 Pages: 248-252
  • DOI: 10.1016/j.alit.2015.01.008
  • NAID: 130005290299
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sensitization of specific IgE-positive Japanese who have experienced Hymenoptera stings to recombinant versions of the Ves v 1 and Ves v 5 allergens in hornet venom (2015)
  • Author(s): Hirata, H., Yoshida,N., Watanabe, M., Sugiyama, K., Arima, M. and Ishii, Y.
  • Journal Title: Allergology International Volume: 64 Issue: 1 Pages: 115-117
  • DOI: 10.1016/j.alit.2014.08.008
  • NAID: 130004873133
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Epidemiologic Investigation of Hornet and Paper Wasp Stings in Forest Workers and Electrical Facility Field Workers in Japan (2014)
  • Author(s): Hayashi, Y., Hirata, H., Watanabe, M., Yoshida, N., Yokoyama, T., Murayama, Y., Sugiyama, K., Arima, M., Fukushima, Y., Fukuda, T. and Ishii, Y.
  • Journal Title: Allergology International Volume: 63 Issue: 1 Pages: 21-26
  • DOI: 10.2332/allergolint.13-OA-0556
  • NAID: 130004873101
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells. (2014)
  • Author(s): Ikari J, Inamine A, Yamamoto T, Watanabe-Takano H, Yoshid a N, Fujimura L, Taniguchi T, Sakamoto A, Hatano M, Tatsumi K, Tokuhisa T, Arima M.
  • Journal Title: Allergy. Volume: 69 Issue: 2 Pages: 223-230
  • DOI: 10.1111/all.12328
  • Peer Reviewed / Open Access
• [Journal Article] Leukotriene C4 aggravates bleomycin-induced pulmonary fibrosis in mice (2013)
  • Author(s): Hirata H, Arima M, Fukushima Y, Sugiyama K, Tokuhisa T, and Fukuda T
  • Journal Title: Respirology Volume: 18 Issue: 4 Pages: 674-681
  • DOI: 10.1111/resp.12072
  • Peer Reviewed
• [Journal Article] Wasp venom allergy: effect of anti-IgE antibody on wasp venom anaphylaxis in a mouse model (2013)
  • Author(s): 46. Ikeno, Y., Hirata, H., Arima, M., Hayashi, Y., Watanabe, M., Yoshida, N., Chibana, K., Sugiyama, K., Fukushima, Y., Akutsu, I. and Fukuda, T.
  • Journal Title: Asian Pac. J Allergy Immunol. Volume: 31 Issue: 2 Pages: 115-124
  • DOI: 10.12932/ap0239.31.2.2013
  • Peer Reviewed
• [Journal Article] Lack of both α2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production (2013)
  • Author(s): Okada K, Ueshima S, Kawao N, Yano M, Tamura Y, Tanaka M, Sakamoto A, Hatano M, Arima M, Miyata S, Nagai N, Tokuhisa T, and Matsuo O
  • Journal Title: Life Sci Volume: 93 Issue: 2-3 Pages: 89-95
  • DOI: 10.1016/j.lfs.2013.05.023
  • Peer Reviewed
• [Journal Article] Monoclonal Antibody against IL-5 Receptor Alpha, but Not IL-5, Inhibits Airway Hyperresponsiveness Associated with Airway Remodeling (2013)
  • Author(s): 48. Obara, K., Sugiyama, K., Hirata, H., Kikkawa, Y., Sakio, H., Arima, M., Fukushima, Y. and Fukuda T.
  • Journal Title: Int. Med. J. Volume: 20 Pages: 579-583
  • Peer Reviewed
• [Journal Article] TH2細胞とTFH細胞におけるIL-4発現誘導機構の相違 (2013)
  • Author(s): 有馬雅史
  • Journal Title: 臨床免疫・アレルギー科 Volume: 59 Pages: 528-536
  • NAID: 40019682612
• [Journal Article] ADAR1 induces adenosine-targeted DNA mutations in senescent Bcl6-deficient cells (2013)
  • Author(s): Tsuruoka, N., Arima, M., Yoshida, N., Okada, S., Sakamoto, A., Hatano, M., Satake, H., Arguni, E., Wang, J.-Y., Yang, J.-H., Nishikura, K., Sekiya, S., Shozu, M. and Tokuhisa, T.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 2 Pages: 826-836
  • DOI: 10.1074/jbc.m112.365718
  • Peer Reviewed
• [Journal Article] Measurement of Hymenoptera venom specific IgE by the IMMULITE 3gAllergy in subjects with negative or positive results by ImmunoCAP (2012)
  • Author(s): M. Watanabe
  • Journal Title: Asia Pac. Allergy. Volume: 2 Issue: 3 Pages: 195-202
  • DOI: 10.5415/apallergy.2012.2.3.195
  • Peer Reviewed
• [Journal Article] 樹状細胞におけるBCL6の発現とヘルパーT細胞の誘導制御 (2012)
  • Author(s): 有馬 雅史
  • Journal Title: 臨床免疫・アレルギー科 Volume: 58 Pages: 517-524
• [Presentation] α2-antiplasmin/PAI-1両遺伝子欠損マウスにおける免疫系の変化についての検討. (2014)
  • Author(s): 上嶋繁, 岡田清孝, 河尾直之, 矢野昌人, 田村行識, 田中勝喜, 坂本明美, 幡野雅彦, 有馬雅史, 宮田清司, 永井信夫, 徳久剛史, 松尾理
  • Organizer: 日本血栓止血学会
  • Place of Presentation: 大阪国際交流センター (大阪府 大阪市）
  • Year and Date: 2014-05-30
• [Presentation] IgE抗体産生機構と制御法の開発
  • Author(s): 徳久剛史、有馬雅史
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Roles of ADAR1 in somatic hypermutation and class switch recombination in germinal center B cells
  • Author(s): Tsuruoka Nobuhide
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Phf11 promotes IgE class switch recombination in activated B cells
  • Author(s): Yamamoto Takuya
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Role of IL-33 in a suppressive function of Bcl6 for IL-4 production by memory Th2 cells
  • Author(s): Arima Masafumi
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Regulation of SLAM-associated protein in follicular helper T cells by Bcl6
  • Author(s): Taniguchi Toshibumi
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場
• [Remarks] 千葉大学大学院医学研究院分化制御学教室
  • URL: http://www.m.chiba-u.ac.jp/class/devgen/
• [Remarks] 千葉大学大学院医学研究院分化制御学教室
  • URL: http://www.m.chiba-u.ac.jp/class/devgen/