Analysis of antibody production program underlying immune-related disorders of human system

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590405
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: ICHIMIYA Shingo 札幌医科大学, 医学部, 教授 (30305221)
• Co-Investigator(Renkei-kenkyūsha): HIMI Tetsuo 札幌医科大学, 医学部, 教授 (90181114) ; SATO Noriyuki 札幌医科大学, 医学部, 教授 (50158937)
• Project Period (FY): 2011 – 2013
• Keywords: 濾胞ヘルパーT細胞 / 免疫アレルギー疾患 / 感染症 / ワクチン開発 / POU2AF1 / 免疫組織 / 睡眠時無呼吸症候群

Research Abstract

Follicular helper T (Tfh) cells play a cardinal role in the production of high-affinity antibodies and their plasticity enables to become other effector helper T cells; however, regulatory mechanism of human Tfh cells is not fully elucidated. In this study we aimed to understand biomedical features of human Tfh cells. Results demonstrated that hypertrophic tonsils of the patients with obstructive sleep apnea syndrome preferentially possessed Tfh cells within enlarged lymphoid follicles. When examined blood Tfh cells of patients with immune-related disorders including allergic rhinitis or asthma, Tfh2 cells were predominantly observed. Thus far unusual manner of Tfh cell differentiation (named Tfh-shift or Tfh2-shift in this study) would be attributable for underlying conditions of such disorders. Further studies should be required, although ALOX5-related lipid mediators and/or POU2AF1 might be involved in the skewed differentiation of human Tfh cells.

Research Products

• [Journal Article] Multifocal and microscopic chromophobe renal cell carcinomatous lesions associated with 'capsulomas' without FCLN gene abnormality (2013)
  • Author(s): Sugimoto K, Takasawa A, Ichimiya S, Murata M, Kimura H, Aoyama T, Gille JJ, Kuroda N, Shimizu H, Hasegawa T, Sawada N, Furuya M, Nagashima Y
  • Journal Title: Pathol Int Volume: 63 Pages: 510-5
  • DOI: 10.1111/pin.12099
  • Peer Reviewed
• [Journal Article] Evaluation of submandibular versus labial salivary gland fibrosis in IgG4-related disease (2013)
  • Author(s): Takano K, Keira Y, Seki N, Abe A, Yamamoto M, Takahashi H, Himi T
  • Journal Title: Mod Rheumatol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] 扁桃・アデノイドはなぜあるのか?鼻はなにをしているのか?小児の粘膜免疫•粘膜防御最前線 (2013)
  • Author(s): 氷見徹夫, 高野賢一, 山下恵司, 小笠原徳子, 正木智之, 小幡和史, 堤裕幸, 小島隆, 一宮慎吾, 澤田典均, 横田伸一
  • Journal Title: 小児耳鼻咽喉科 Volume: 34(3) Pages: 239-244
• [Journal Article] Tfh細胞とBメモリーB細胞 (2013)
  • Author(s): 一宮慎吾, 山下恵司, 長屋朋典, 三橋由佳梨, 松宮弘, 長島勉, 氷見徹夫
  • Journal Title: 臨床免疫•アレルギー科 Volume: 60(4) Pages: 576-580
• [Journal Article] Sorting nexin 5 of a new diagnostic marker of papillary thyroid carcinoma regulates Caspase-2 (2012)
  • Author(s): Ara S, Kikuchi T, Matsumiya H, Kojima T, Kubo T, Ye RC, Sato A, Kon S, Honma T, Asakura K, Hasegawa T, Himi T, Sato N, Ichimiya S
  • Journal Title: Cancer Sci Volume: 103 Pages: 1356-62
  • DOI: 10.1111/j.1349-7006.2012.02296.x
  • Peer Reviewed
• [Journal Article] The role of IL-33 and its receptor ST2 in human nasal epithelium with allergic rhinitis (2012)
  • Author(s): Kamekura R, Kojima T, Takano K, Go M, Sawada N, Himi T
  • Journal Title: Clin Exp Allergy Volume: 42 Pages: 218-28
  • DOI: 10.1111/j.1365-2222.2011.03867.x
  • Peer Reviewed
• [Journal Article] Anti-CADM-140 antibody positive juvenile dermatomyositis with rapidly progressive interstitial lung disease and cardiac involvement (2011)
  • Author(s): Sakurai N, Nagai K, Tsutsumi H, Ichimiya S
  • Journal Title: J Rheumatol Volume: 38 Pages: 963-4
  • DOI: 10.3899/jrheum.101220
  • Peer Reviewed
• [Journal Article] Arachidonate 5-lipoxygenase establishes adaptive humoral immunity by controlling primary B cells and their cognate T-cell help (2011)
  • Author(s): Nagashima T, Ichimiya S, Kikuchi T, Saito Y, Matsumiya H, Ara S, Koshiba S, Zhang J, Hatate C, Tonooka A, Kubo T, Ye RC, Hirose B, Shirasaki H, Izumi T, Takami T, Himi T, Sato N
  • Journal Title: Am J Pathol Volume: 178 Pages: 222-32
  • DOI: 10.1016/j.ajpath.2010.11.033
  • Peer Reviewed
• [Journal Article] Epithelial barrier and antigen uptake in lymphoepithelium of human adenoids (2011)
  • Author(s): Ogasawara N, Kojima T, Go M, Takano K, Kamekura R, Ohkuni T, Koizumi J, Masaki T, Fuchimoto J, Obata K, Kurose M, Shintani T, Sawada N, Himi T
  • Journal Title: Acta Otolaryngol Volume: 131 Pages: 116-23
  • DOI: 10.3109/00016489.2010.520022
  • Peer Reviewed
• [Journal Article] Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients (2011)
  • Author(s): Kameshima H, Tsuruma T, Torigoe T, Takahashi A, Hirohashi Y, Tamura Y, Tsukahara T, Ichimiya S, Kanaseki T, Iwayama Y, Sato N, Hirata K
  • Journal Title: Cancer Sci Volume: 102 Pages: 1181-7
  • DOI: 10.1111/j.1349-7006.2011.01918.x
  • Peer Reviewed
• [Journal Article] Poly(I : C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-αvia distinct NF-κB pathways in human nasal epithelial cells (2011)
  • Author(s): Ohkuni T, Kojima T, Ogasawara N, Masaki T, Fuchimoto J, Kamekura R, Koizumi J, Ichimiya S, Murata M, Tanaka S, Himi T, Sawada N
  • Journal Title: Toxicol Appl Pharmacol Volume: 250 Pages: 29-38
  • DOI: 10.1016/j.taap.2010.09.023
  • Peer Reviewed
• [Presentation] 濾胞ヘルパーT細胞の分化機構と免疫病態との関連 (2014)
  • Author(s): 長屋朋典, 亀倉隆太, 山下恵司, 三橋由佳梨, 熊谷綾子, 長島勉, 一宮慎吾, 氷見徹夫
  • Organizer: 第32回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 徳島市
  • Year and Date: 20140206-08
• [Presentation] 扁桃濾胞ヘルパーT細胞におけるPOU2AF1の機構解析 (2014)
  • Author(s): 山下恵司, 松宮弘, 三橋由佳梨, 長屋朋典, 亀倉隆太, 関伸彦, 一宮慎吾, 氷見徹夫
  • Organizer: 第32回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 徳島市
  • Year and Date: 20140206-08
• [Presentation] Functional significance of POU2AF1 in the regulation of follicular helper T cells (2013)
  • Author(s): Yamashita K, Mitsuhashi Y, Nagaya T, Kamekura R, Seki N, Kumagai A, Himi T, Ichimiya S
  • Organizer: Annual Meeting of the Japanese Society of Immunology 2013
  • Place of Presentation: Chiba, Japan
  • Year and Date: 20131211-13
• [Presentation] Np63 controls a TLR3-mediated mechanism that abundantly provides thymic stromal lymphopoietin in atopic dermatitis (2013)
  • Author(s): Kubo T, Kumagai A, Yamashita K, Nagaya T, Mitsuhashi Y, Sato N, Yamashita T, Himi T, Ichimiya S
  • Organizer: 6th p63/p73 Workshop
  • Place of Presentation: Chiba, Japan
  • Year and Date: 20130915-18
• [Presentation] POU2AF1 regulates follicular helper T cells of human tontils (2013)
  • Author(s): Yamahita K, Mitsuhashi Y, Nagaya T, Seki N, Ogasawarea N, Okuni T, Takano K, Ichimiya S, Himi T
  • Organizer: 8th International Symposium on Tonsils and Mucosal Barriers of the Upper Airways
  • Place of Presentation: Zurich, Switzerland
  • Year and Date: 20130717-19
• [Presentation] 濾胞ヘルパーT細胞を調節すPOU2AF1の機構的意義 (2013)
  • Author(s): 山下恵司, 松宮弘, 三橋由佳梨, 関伸彦, 佐藤昇志, 氷見徹夫, 一宮慎吾
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌市
  • Year and Date: 20130606-08
• [Presentation] アトピー型気管支喘息患者における血清IL-9の検討 (2012)
  • Author(s): 重原克則, 伊藤進, 井上祐二, 一宮慎吾
  • Organizer: 第62回日本アレルギー学会秋期学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 20121129-1201
• [Presentation] アトピー性皮膚炎の表皮におけるp63依存性TSLP-TSLP受容体経路 (2012)
  • Author(s): 久保輝文, 三橋由佳梨, 山下恵司, 佐藤明紀, 小島隆, 佐藤昇志, 一宮慎吾
  • Organizer: 第40回日本臨床免疫学会総会
  • Place of Presentation: 東京都
  • Year and Date: 20120927-29
• [Presentation] POU2AF1(+)濾胞ヘルパーT細胞による閉塞性睡眠時無呼吸症候群の病態形成 (2012)
  • Author(s): 山下恵司, 関伸彦, 松宮弘, 三橋由佳梨, 荒志保子, 久保輝文, 一宮慎吾, 氷見徹夫
  • Organizer: 第26回日本口腔•咽頭科学会総会
  • Place of Presentation: 熊本市
  • Year and Date: 20120911-12
• [Presentation] 進行性筋萎縮症(PMA)の1剖検例における異常TDP-43 (2012)
  • Author(s): 山内理香, 山本大輔, 岩原直敏, 津田玲子, 松村晃寛, 鈴木秀一郎, 津田笑子, 保月隆良, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊, 杉本幸太郎, 一宮慎吾, 長谷川匡
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 20120522-25
• [Presentation] 閉塞性睡眠時無呼吸症候群の扁桃肥大メカニズムと濾胞ヘルパーT細胞との関連 (2012)
  • Author(s): 松宮弘, 荒志保子, 久保輝文, 一宮慎吾, 氷見徹夫
  • Organizer: 第113回日本耳鼻咽喉科学会総会
  • Place of Presentation: 新潟市
  • Year and Date: 20120510-12
• [Presentation] 甲状腺乳頭癌におけるSNX5の機能解析 (2012)
  • Author(s): 荒志保子, 松宮弘, 久保輝文, 一宮慎吾, 氷見徹夫
  • Organizer: 第113回日本耳鼻咽喉科学会総会
  • Place of Presentation: 新潟市
  • Year and Date: 20120510-12
• [Presentation] A novel autocrine-paracrine loop of TSLP in atopic dermatitis is regulated by p63 (2012)
  • Author(s): Kubo T, Ye RC, Ara S, Matsumiya H, Kojima T, Kikuchi T, Sato N, Ichimiya S
  • Organizer: 99th Annual Meeting of the American Association of Immunologists
  • Place of Presentation: Boston, USA
  • Year and Date: 20120504-08
• [Presentation] POU2AF1(+) follicular helper T cells in obstructive sleep apnea syndrome (2012)
  • Author(s): Ichimiya S, Matsumiya H, Kubo T, Ara S, Ye RC, Sato A, Kikuchi T, Yamashita K, Mitsuhashi Y, Seki N, Shirasaki H, Kimura S, Yokoyama S, Sato N, Himi T
  • Organizer: 99th Annual Meeting of the American Association of Immunologists
  • Place of Presentation: Boston, USA
  • Year and Date: 20120504-08
• [Presentation] 表皮幹細胞因子p63はケラチノサイトにおけるTSLP受容体の発現を制御する (2012)
  • Author(s): 久保輝文, Ye RC, 松宮弘, 荒志保子, 小島隆, 佐藤昇志, 一宮慎吾
  • Organizer: 第101回日本病理学会総会
  • Year and Date: 20120426-28
• [Presentation] Epidermal stem cell factor p63 regulates thymic stromal lymphopoietin receptor (TSLPR): a putative role of TSLP in the pathogenesis of atopic dermatitis (2011)
  • Author(s): Kubo T, Ara S, Ye RC, Matsumiya H, Kojima T, Sato N, Ichimiya S
  • Organizer: Annual Meeting of the Japanese Society of Immunology 2011
  • Place of Presentation: Chiba, Japan
  • Year and Date: 20111127-29
• [Presentation] The regulatory mechanism of follicular helper T cells in humoral memory response (2011)
  • Author(s): Matsumiya H, Ara S, Kubo T, Ye RC, Himi T, Sato N, Ichimiya S
  • Organizer: Annual Meeting of the Japanese Society of Immunology 2011
  • Place of Presentation: Chiba, Japan
  • Year and Date: 20111127-29
• [Presentation] Lシリーズ抗ヒトリンパ球抗体の有用性とその抗原系の解析.学術研究賞演説(A演説) (2011)
  • Author(s): 一宮慎吾
  • Organizer: 第57回日本病理学会秋期特別総会
  • Place of Presentation: 東京
  • Year and Date: 20111117-18
• [Presentation] Functional significance of the expression of sorting nexin family in thyroid papillary cancer (2011)
  • Author(s): Ara S, Ichimiya S, Kubo T, Matsumiya H, Ye RC, Sato N, Kojima T, Hasegawa T, Himi T, Kikuchi T, Kon S
  • Organizer: 第70回日本癌学会総会.
  • Place of Presentation: 名古屋市
  • Year and Date: 20111003-05
• [Presentation] 閉塞性睡眠時無呼吸症候群の扁桃組織における濾胞ヘルパーT細胞の機能解析 (2011)
  • Author(s): 松宮弘, 荒志保子, 久保輝文, Ye RC, 一宮慎吾, 氷見徹夫
  • Organizer: 第24回日本口腔咽頭科学会総会
  • Place of Presentation: 広島市
  • Year and Date: 20110908-09
• [Presentation] 甲状腺乳頭癌におけるSNXファミリーの機能解析.(優秀ポスター賞) (2011)
  • Author(s): 荒志保子, 一宮慎吾, 久保輝文, 松宮弘, Ye RC, 佐藤昇志, 小島隆, 長谷川匡, 氷見徹夫, 菊地智樹, 今信一郎
  • Organizer: 第8回日本病理学会カンファレンス
  • Place of Presentation: 松本市
  • Year and Date: 20110805-06
• [Presentation] 表皮ケラチノサイトに発現するTSLP受容体がアトピー性皮膚炎病態に果たす役割の検討 (2011)
  • Author(s): 久保輝文, 荒志保子, Ye RC, 松宮弘, 小島隆, 佐藤昇志, 一宮慎吾
  • Organizer: 第8回日本病理学会カンファレンス
  • Place of Presentation: 松本市
  • Year and Date: 20110805-06
• [Presentation] 死後画像診断と病理解剖所見の比較 (2011)
  • Author(s): 兵頭秀樹, 佐藤大志, 兵頭かずさ, 玉川光春, 山直也, 計良淑子, 一宮慎吾, 長谷川匡, 晴山雅人
  • Organizer: 第70回日本医学放射線学会総会Web開催
  • Year and Date: 20110509-20
• [Presentation] アレルギー疾患における免疫細胞としての上皮の役割 (2011)
  • Author(s): 久保輝文, 一宮慎吾, Ye RC, 松宮弘, 荒志保子, 佐藤昇志
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 20110428-30
• [Book] B細胞と脂質メディエーター.上気道炎症における鼻粘膜の役割.氷見徹夫編 (2012)
  • Author(s): 長島勉, 荒志保子, 一宮慎吾
  • Total Pages: 156-163
  • Publisher: アイワード札幌
• [Book] 粘膜関連リンパ組織と濾胞ヘルパーT細胞.氷見徹夫編 (2012)
  • Author(s): 松宮弘, 三橋由佳梨, 山下恵司, 一宮慎吾
  • Total Pages: 194-204
  • Publisher: アイワード札幌
• [Remarks] 札幌医科大学医学部附属フロンティア医学 研究所免疫制御医学部門
  • URL: http://web.sapmed.ac.jp/immunology/index.html