The development of immune-modulate molecule using the binding specificity of Toll-Interleukin-1 receptor domain

• Project/Area Number: 23791161
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: OHNISHI Hidenori 岐阜大学, 医学(系)研究科(研究院), 助教 (60381620)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 自然免疫

Research Abstract

In this study, we aimed the development of the molecule, which modulates the Toll-Interleukin-1 receptor (TIR) signaling using the binding specificity of TIR domain of MyD88. The dominant negative form (DN) of MyD88 fused with protein transduction domain (PTD) was purified with E. Coli protein expression system. In order to stabilize this protein, two cysteine amino acids of MyD88, C203 and C280, were mutated to serine (CS). PTD-MyD88-DN-CS protein caused the ligand-independent increase of transcriptional activity of NF-kappaB.

Research Products

• [Journal Article] Functional assessment of the mutational effects of human IRAK4 and MyD88 genes (2014)
  • Author(s): Yamamoto T, Tsutsumi N, Tochio H, Ohnishi H, Kubota K, Kato Z, Shirakawa M, Kondo N
  • Journal Title: Mol Immunol Volume: 58(1) Pages: 66-76
  • Peer Reviewed
• [Journal Article] Functional assessment of the mutational effects of human IRAK4 and MyD88 genes. (2014)
  • Author(s): Yamamoto T, Tsutsumi N, Tochio H, Ohnishi H, Kubota K, Kato Z, Shirakawa M, Kondo N.
  • Journal Title: Mol Immunol Volume: 58(1) Issue: 1 Pages: 66-76
  • DOI: 10.1016/j.molimm.2013.11.008
  • Peer Reviewed
• [Journal Article] Hyporesponsiveness to the infecting serotype after vaccination of children with seven-valent pneumococcal conjugate vaccine following invasive pneumococcal disease. (2014)
  • Author(s): Tamura K, Matsubara K, Ishiwada N, Nishi J, Ohnishi H, Suga S, Ihara T, Chang B, Akeda Y, Oishi K
  • Journal Title: Vaccine Volume: 32 Pages: 1444-1450
  • Peer Reviewed
• [Journal Article] Pediatric allergy and immunology in Japan (2013)
  • Author(s): Ebisawa M, Nishima S, Ohnishi H, Kondo N
  • Journal Title: Pediatr Allergy Immunol Volume: 24(7) Pages: 704-14
  • Peer Reviewed
• [Journal Article] Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency caused by a novel NFKBIA mutation, p.Ser36Tyr, presents with mild ectodermal dysplasia and non-infectious systemic inflammation (2013)
  • Author(s): Yoshioka T, Nishikomori R, Hara J, Okada K, Hashii Y, Okafuji I, Nodomi S, Kawai T, Izawa K, Ohnishi H, Yasumi T, Nakahata T, Heike T
  • Journal Title: J Clin Immunol Volume: 33(7) Pages: 1165-74
  • Peer Reviewed
• [Journal Article] In vitro analysis of the functional effects of an NLRP3 G809S variant with the co-existence of MEFV haplotype variants in atypical autoinflammatory syndrome (2013)
  • Author(s): Kubota K, Ohnishi H, Teramoto T, Matsui E, Murase K, Kanoh H, Kato Z, Kaneko H, Seishima M, Kondo N
  • Journal Title: J Clin Immunol Volume: 33(2) Pages: 325-34
  • Peer Reviewed
• [Journal Article] Pediatric allergy and immunology in Japan. (2013)
  • Author(s): Ebisawa M, Nishima S, Ohnishi H, Kondo N.
  • Journal Title: Pediatr Allergy Immunol. Volume: 24 Issue: 7 Pages: 704-714
  • DOI: 10.1111/pai.12117
  • Peer Reviewed
• [Journal Article] Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency caused by a novel NFKBIA mutation, p.Ser36Tyr, presents with mild ectodermal dysplasia and non-infectious systemic inflammation. (2013)
  • Author(s): Yoshioka T, Nishikomori R, Hara J, Okada K, Hashii Y, Okafuji I, Nodomi S, Kawai T, Izawa K, Ohnishi H, Yasumi T, Nakahata T, Heike T.
  • Journal Title: J Clin Immunol. Volume: 33 Issue: 7 Pages: 1165-1174
  • DOI: 10.1007/s10875-013-9924-z
  • Peer Reviewed
• [Journal Article] In vitro analysis of the functional effects of an NLRP3 G809S variant with the co-existence of MEFV haplotype variants in atypical autoinflammatory syndrome. (2013)
  • Author(s): Kubota K, Ohnishi H, Teramoto T, Matsui E, Murase K, Kanoh H, Kato Z, Kaneko H, Seishima M, Kondo N
  • Journal Title: J Clin Immunol Volume: 33 Pages: 325-334
  • Peer Reviewed
• [Journal Article] Autosomal-dominant chronic mucocutaneous candidiasis with STAT1-mutation can be complicated with chronic active hepatitis and hypothyroidism (2012)
  • Author(s): Hori T, Ohnishi H, Teramoto T, Tsubouchi K, Naiki T, Hirose Y, Ohara O, Seishima M, Kaneko H, Fukao T, Kondo N
  • Journal Title: J Clin Immunol Volume: 32(6) Pages: 1213-20
  • Peer Reviewed
• [Journal Article] Molecular analysis of the binding mode of Toll/interleukin-1 receptor (TIR) domain proteins during TLR2 signaling (2012)
  • Author(s): Nada M, Ohnishi H, Tochio H, Kato Z, Kimura T, Kubota K, Yamamoto T, Kamatari YO, Tsutsumi N, Shirakawa M, Kondo N
  • Journal Title: Mol Immunol Volume: 52(3-4) Pages: 108-16
  • Peer Reviewed
• [Journal Article] TRAM is involved in IL-18 signaling and functions as a sorting adaptor for MyD88 (2012)
  • Author(s): Ohnishi H, Tochio H, Kato Z, Kawamoto N, Kimura T, Kubota K, Yamamoto T, Funasaka T, Nakano H, Wong RW, Shirakawa M, Kondo N
  • Journal Title: PLoS One Volume: 7(6)
  • NAID: 120005540726
  • Peer Reviewed
• [Journal Article] Characterization of NLRP3 variants in Japanese cryopyrin-associated periodic syndrome patients (2012)
  • Author(s): Ohnishi H, Teramoto T, Iwata H, Kato Z, Kimura T, Kubota K, Nishikomori R, Kaneko H, Seishima M, Kondo N
  • Journal Title: J Clin Immunol Volume: 32(2) Pages: 221-9
  • Peer Reviewed
• [Journal Article] Structural property of soybean protein P34 and specific IgE response to recombinant P34 in patients with soybean allergy (2012)
  • Author(s): Morita H, Kaneko H, Ohnishi H, Kato Z, Kubota K, Yamamoto T, Matsui E, Teramoto T, Fukao T, Kasahara K, Kondo N
  • Journal Title: Int J Mol Med Volume: 29(2) Pages: 153-8
  • Peer Reviewed
• [Journal Article] A rapid screening method to detect autosomal-dominant ectodermal dysplasia with immune deficiency syndrome (2012)
  • Author(s): Ohnishi H, Miyata R, Suzuki T, Nose T, Kubota K, Kato Z, Kaneko H, Kondo N
  • Journal Title: J Allergy Clin Immunol Volume: 129(2) Pages: 578-80
  • NAID: 10030801132
  • Peer Reviewed
• [Journal Article] Autosomal-dominant chronic mucocutaneous candidiasis with STAT1-mutation can be complicated with chronic active hepatitis and hypothyroidism. (2012)
  • Author(s): Hori T, Ohnishi H, Teramoto T, Tsubouchi K, Naiki T, Hirose Y, Ohara O, Seishima M, Kaneko H, Fukao T, Kondo N.
  • Journal Title: J Clin Immunol Volume: 32 Pages: 1213-1220
  • Peer Reviewed
• [Journal Article] TRAM is involved in IL-18 signaling and functions as a sorting adaptor for MyD88. (2012)
  • Author(s): Ohnishi H, Tochio H, Kato Z, Kawamoto N, Kimura T, Kubota K, Yamamoto T, Funasaka T, Nakano H, Wong RW, Shirakawa M, Kondo N.
  • Journal Title: PLoS One Volume: 7
  • NAID: 120005540726
  • Peer Reviewed
• [Journal Article] Molecular analysis of the binding mode of Toll/interleukin-1 receptor (TIR) domain proteins during TLR2 signaling (2012)
  • Author(s): Nada M, Ohnishi H, Tochio H, Kato Z, Kimura T, Kubota K, Yamamoto T, Kamatari YO, Tsutsumi N, Shirakawa M, Kondo N.
  • Journal Title: Mol Immunol. Volume: 52 Pages: 108-116
  • Peer Reviewed
• [Journal Article] Characterization of NLRP3 Variants in Japanese Cryopyrin-Associated Periodic Syndrome Patients. (2012)
  • Author(s): Ohnishi H, Teramoto T, Iwata H, Kato Z, Kimura T, Kubota K, Nishikomori R, Kaneko H, Seishima M, Kondo N.
  • Journal Title: J Clin Immunol. Volume: 32 Pages: 221-229
  • Peer Reviewed
• [Journal Article] Structural property of soybean protein P34 and specific IgE response to recombinant P34 in patients with soybean allergy. (2012)
  • Author(s): Morita H, Kaneko H, Ohnishi H, Kato Z, Kubota K, Yamamoto T, Matsui E, Teramoto T, Fukao T, Kasahara K, Kondo N.
  • Journal Title: Int J Mol Med. Volume: 29 Pages: 153-158
  • Peer Reviewed
• [Journal Article] A rapid screening method to detect autosomal-dominant ectodermal dysplasia with immune deficiency syndrome. (2012)
  • Author(s): Ohnishi H, Miyata R, Suzuki T, Nose T, Kubota K, Kato Z, Kaneko H, Kondo N.
  • Journal Title: J Allergy Clin Immunol. Volume: 129 Pages: 578-580
  • NAID: 10030801132
  • Peer Reviewed
• [Journal Article] Refractory chronic pleurisy caused by Helicobacter equorum-like bacterium in a patient with X-linked agammaglobulinemia (2011)
  • Author(s): Funato M, Kaneko H, Ohkusu K, Sasai H, Kubota K, Ohnishi H, Kato Z, Fukao T, Kondo N
  • Journal Title: J Clin Microbiol Volume: 49(9) Pages: 3432-5
  • Peer Reviewed
• [Journal Article] Refractory chronic pleurisy caused by Helicobacter equorum-like bacterium in a patient with X-linked agammaglobulinemia. (2011)
  • Author(s): Funato M, Kaneko H, Ohkusu K, Sasai H, Kubota K, Ohnishi H, Kato Z, Fukao T, Kondo N.
  • Journal Title: J Clin Microbiol. Volume: 49 Pages: 3432-3435
  • Peer Reviewed
• [Journal Article] 皮膚症状からみた自己炎症性症候群 (2011)
  • Author(s): 大西秀典、寺本貴英、久保田一生、清島真理子、近藤直実
  • Journal Title: 小児皮膚科学会雑誌 Volume: 30 Pages: 11-16
  • NAID: 10029837057
• [Presentation] Characterization of NLRP3 Variants in Japanese Cryopyrin-associated Periodic Syndrome Patients (2012)
  • Author(s): Hidenori Ohnishi, Takahide Teramoto, Zenichiro Kato, Kazuo Kubota, Hideo Kaneko, and Naomi Kondo
  • Organizer: UTOIMMUNITY 2012(第8回国際自己免疫疾患学会)
  • Place of Presentation: Granada, Spain
• [Presentation] Molecular analysis of signal transduction pathway of IL-18, related with allergic condition (2012)
  • Author(s): Hidenori Ohnishi, Zenichiro Kato, Takeshi Kimura, Kazuo Kubota, Takahiro Yamamoto, Naomi Kondo
  • Organizer: The 22nd Congress of Interasma Japan / North Asia
  • Place of Presentation: Fukuoka Japan
• [Presentation] The functional assessments of mutational effect of human IRAK4 and MyD88 gene (2012)
  • Author(s): Hidenori Ohnishi, Naotaka Tsutsumi, Takahiro Yamamoto, Hidehito Tochio, Zenichiro Kato, Kazuo Kubota, Masahiro Shirakawa, Naomi Kondo
  • Organizer: APAPARI 2012
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Gene polymorphisms in innate immune signaling pathways associated with allergic disease (2011)
  • Author(s): Hidenori Ohnishi
  • Organizer: Asia Pacific Association of Pediatric Allergy, Respirology and Immunology 2011 (APAPARI 2011), 48th Annual Meeting of Japanese Society of Pediatric Allergy and Clinical Immunoligy (48th JSPACI)
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Gene polymorphisms in innate immune signaling pathways associated with allergic disease (2011)
  • Author(s): Ohnishi H
  • Organizer: Asia Pacific Association of Pediatric Allergy, Respirology and Immunology2011 (APAPARI 2011) 48th Annual Meeting of Japanese Society of Pediatric Allergy and Clinical Immunoligy (48 th JSPACI)
  • Place of Presentation: Fukuoka
• [Presentation] 自然免疫不全症の病態解明と診断手順について (2011)
  • Author(s): 大西秀典
  • Organizer: 第6回岐阜小児アレルギー・喘息研究会
  • Place of Presentation: 岐阜
• [Presentation] インターロイキン18 シグナル伝達経路の分子生物学的解析 (2011)
  • Author(s): 大西秀典
  • Organizer: 第61回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
• [Presentation] フローサイトメーターによるスクリーニング法で診断された新規遺伝子変異を有するIκBα欠損症の1男児例 (2011)
  • Author(s): 大西秀典、加藤善一郎、金子英雄、近藤直実、宮田理英、鈴木智典、能勢統一郎
  • Organizer: 春期日本アレルギー学会(第23回)
  • Place of Presentation: 千葉
• [Presentation] 自然免疫不全症の構造生物学的病態解析 (2011)
  • Author(s): 大西秀典、加藤善一郎、安陽、松井永子、木村豪、名田匡利、久保田一生、山本崇裕、金子英雄、近藤直実
  • Organizer: 日本小児科学会(第114回)
  • Place of Presentation: 東京
• [Presentation] IRAK4ミスセンス遺伝子変異の病的意義の判定方法 (2011)
  • Author(s): 大西秀典、山本崇裕、加藤善一郎、近藤直実
  • Organizer: 日本免疫学会(第40回)
  • Place of Presentation: 千葉
• [Book] メバロン酸キナーゼ欠損症別冊日本臨床先天代謝異常症候群(第2版)上 (2012)
  • Author(s): 深尾敏幸、大西秀典
  • Publisher: 日本臨床社
• [Book] 原発性免疫不全症の概念と分類,および自己炎症性疾患・自然免疫不全症・近縁疾患の位置づけ自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 近藤直実、大西秀典、渡邉倫子
  • Publisher: 診断と治療社
• [Book] 自己炎症性疾患・自然免疫不全症の病因・病態と診断フローチャート自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 大西秀典
  • Publisher: 診断と治療社
• [Book] 自己炎症性疾患総論自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 加藤善一郎、大西秀典、近藤直実
  • Publisher: 診断と治療社
• [Book] 自然免疫不全症総論自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 大西秀典
  • Publisher: 診断と治療社
• [Book] ヒトパピローマウイルス易感染症自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 加藤善一郎、大西秀典、近藤直実
  • Publisher: 診断と治療社
• [Book] (家族性)単純ヘルペス脳炎自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 久保田一生、山本崇裕、大西秀典
  • Publisher: 診断と治療社
• [Book] 慢性皮膚粘膜カンジダ症を伴う免疫不全症自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 堀友博、大西秀典
  • Publisher: 診断と治療社
• [Book] カンジダ感染と外胚葉異形成を伴う自己免疫性多腺性内分泌不全症自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 堀友博、大西秀典
  • Publisher: 診断と治療社
• [Book] Castleman病自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 寺本貴英、大西秀典、近藤直実
  • Publisher: 診断と治療社
• [Book] 慢性皮膚粘膜カンジダ症(STAT1異常症)自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 堀友博、大西秀典
  • Publisher: 診断と治療社
• [Book] 易肺炎球菌感染症自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 大西秀典
  • Publisher: 診断と治療社
• [Book] MEFV遺伝子と炎症性疾患自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 久保田一生、大西秀典
  • Publisher: 診断と治療社
• [Book] 免疫異常疾患に対する免疫療法と抗体療法-その3-自己炎症性疾患に対する生物学的製剤アレルギー疾患の免疫療法と分子標的治療 (2012)
  • Author(s): 大西秀典
  • Publisher: 診断と治療社