Role of airway mucosal IgA in allergic diseases

• Project/Area Number: 17K09629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Teikyo University
• Principal Investigator: Suzukawa Maho 帝京大学, 医学部, 助手 (20453699)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: IgA / 肺線維芽細胞 / 特発性肺線維症 / サイトカイン / CD71 / 気道上皮細胞 / 細胞増殖 / TfR / 喘息 / アレルギー・ぜんそく / 呼吸器内科 / 免疫

Outline of Final Research Achievements

The precise effects of IgA on lung fibroblasts remain unclear. This study aimed to elucidate how IgA activates human lung fibroblasts. Secretory IgA (sIgA) induced interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production by normal human lung fibroblasts (NHLFs). sIgA also promoted proliferation of NHLFs. Among known IgA receptors, NHLFs significantly expressed CD71. Immunohistochemistry revealed that sIgA is abundant in lung sections from patients with idiopathic pulmonary fibrosis (IPF). Our findings suggest that sIgA may promote human lung inflammation by activating human lung fibroblasts.

Academic Significance and Societal Importance of the Research Achievements

気道粘膜を含め生体内において大量に存在する免疫グロブリンであり、抗原曝露の第一線に存在するIgAは、元来生体防御因子として重要視されてきたが、本研究から、肺の炎症を増強することで病原性役割があることが示唆された。本研究の結果を踏まえて、IgAが肺線維芽細胞を活性化する機構を明らかにできれば、IgAの役割の一部を標的とした予防あるいは治療戦略の確立につながる可能性がある。

Research Products

• [Journal Article] Evaluation of cytokine levels using QuantiFERON-TB Gold Plus in patients with active tuberculosis (2020)
  • Author(s): Suzukawa Maho、Takeda Keita、Akashi Shunsuke、Asari Isao、Kawashima Masahiro、Ohshima Nobuharu、Inoue Eri、Sato Ryota、Shimada Masahiro、Suzuki Junko、Yamane Akira、Tamura Atsuhisa、Ohta Ken、Tohma Shigeto、Teruya Katsuji、Nagai Hideaki
  • Journal Title: Journal of Infection Volume: 80 Issue: 5 Pages: 547-553
  • DOI: 10.1016/j.jinf.2020.02.007
  • Peer Reviewed
• [Journal Article] A case of Mycobacterium tuberculosis laboratory cross-contamination (2019)
  • Author(s): Takeda Keita、Murase Yoshiro、Kawashima Masahiro、Suzukawa Maho、Suzuki Junko、Yamane Akira、Igarashi Yuriko、Chikamatsu Kinuyo、Morishige Yuta、Aono Akio、Yamada Hiroyuki、Takaki Akiko、Tamura Atsuhisa、Nagai Hideaki、Matsui Hirotoshi、Tohma Shigeto、Mitarai Satoshi
  • Journal Title: Journal of Infection and Chemotherapy Volume: 25 Issue: 8 Pages: 610-614
  • DOI: 10.1016/j.jiac.2019.03.012
  • Peer Reviewed
• [Journal Article] IL-9 Blockade Suppresses Silica-induced Lung Inflammation and Fibrosis in Mice (2019)
  • Author(s): Sugimoto Naoya、Suzukawa Maho、Nagase Hiroyuki、Koizumi Yuta、Ro Shoki、Kobayashi Konomi、Yoshihara Hisanao、Kojima Yasuhiro、Kamiyama-Hara Asae、Hebisawa Akira、Ohta Ken
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology Volume: 60 Issue: 2 Pages: 232-243
  • DOI: 10.1165/rcmb.2017-0287oc
  • Peer Reviewed
• [Journal Article] Secretory IgA accumulated in the airspaces of idiopathic pulmonary fibrosis and promoted VEGF, TGF‐β and IL‐8 production by A549 cells (2019)
  • Author(s): Kobayashi K.、Suzukawa M.、Watanabe K.、Arakawa S.、Igarashi S.、Asari I.、Hebisawa A.、Matsui H.、Nagai H.、Nagase T.、Ohta K.
  • Journal Title: Clinical & Experimental Immunology Volume: 199 Issue: 3 Pages: 326-336
  • DOI: 10.1111/cei.13390
  • Peer Reviewed
• [Journal Article] Secretory immunoglobulin A induces human lung fibroblasts to produce inflammatory cytokines and undergo activation (2019)
  • Author(s): Arakawa S.、Suzukawa M.、Watanabe K.、Kobayashi K.、Matsui H.、Nagai H.、Nagase T.、Ohta K.
  • Journal Title: Clinical & Experimental Immunology Volume: 195 Issue: 3 Pages: 287-301
  • DOI: 10.1111/cei.13253
  • Peer Reviewed
• [Journal Article] Leptin enhances cytokine/chemokine production by normal lung fibroblasts by binding to leptin receptor (2019)
  • Author(s): Watanabe Kaoru、Suzukawa Maho、Arakawa Sayaka、Kobayashi Koichi、Igarashi Sayaka、Tashimo Hiroyuki、Nagai Hideaki、Tohma Shigeto、Nagase Takahide、Ohta Ken
  • Journal Title: Allergology International Volume: 68 Issue: Supplement.1 Pages: S3-S8
  • DOI: 10.1016/j.alit.2019.04.002
  • NAID: 130007709724
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Allergy to carminic acid: in vitro evidence of involvement of protein-binding hapten (2019)
  • Author(s): Osumi Mika、Yamaguchi Masao、Sugimoto Naoya、Suzukawa Maho、Arai Hidenori、Akiyama Hiroshi、Nagase Hiroyuki、Ohta Ken
  • Journal Title: Asia Pacific Allergy Volume: 9 Issue: 1 Pages: e2-e2
  • DOI: 10.5415/apallergy.2019.9.e2
  • Peer Reviewed
• [Journal Article] Resequencing Study Confirms Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis (2019)
  • Author(s): Moore C, Blumhagen Z, Yang V,Walts A, Powers J, Walker T, Bishop M, Russell P, Vestal B, Cardwell J, Markin CR, Mathai SK, Schwarz MI, Steele MP, Lee J, Brown KK, Loyd JE, Crapo JD, Silverman EK, Cho MH, et al.
  • Journal Title: American Journal of Respiratory and Critical Care Medicine Volume: 印刷中 Issue: 2 Pages: 199-208
  • DOI: 10.1164/rccm.201810-1891oc
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] IL-33, IL-25 and TSLP contribute to development of fungal-associated protease-induced innate-type airway inflammation (2018)
  • Author(s): Hiraishi Yoshihisa、Yamaguchi Sachiko、Yoshizaki Takamichi、Nambu Aya、Shimura Eri、Takamori Ayako、Narushima Seiko、Nakanishi Wakako、Asada Yosuke、Numata Takafumi、Suzukawa Maho、Yamauchi Yasuhiro、Matsuda Akira、Arae Ken、Morita Hideaki、Hoshino Tomoaki、Suto Hajime、Okumura Ko、Matsumoto Kenji、Nakae Susumu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 18052-18052
  • DOI: 10.1038/s41598-018-36440-x
  • Peer Reviewed / Open Access
• [Journal Article] Expression of Siglec-8 is regulated by interleukin-5, and serum levels of soluble Siglec-8 may predict responsiveness of severe eosinophilic asthma to mepolizumab (2018)
  • Author(s): Arakawa Sayaka、Suzukawa Maho、Ohshima Nobuharu、Tashimo Hiroyuki、Asari Isao、Matsui Hirotoshi、Kobayashi Nobuyuki、Shoji Shunsuke、Nagase Takahide、Ohta Ken
  • Journal Title: Allergology International Volume: 67 Issue: Supplement.1 Pages: S41-S44
  • DOI: 10.1016/j.alit.2018.03.006
  • NAID: 130007485210
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab. (2018)
  • Author(s): Suzukawa M, Matsumoto H, et al.
  • Journal Title: Respir Med Volume: 134 Pages: 95-102
  • DOI: 10.1016/j.rmed.2017.12.002
  • Peer Reviewed
• [Journal Article] TBX4 is involved in the super-enhancer-driven transcriptional programs underlying features specific to lung fibroblasts. (2018)
  • Author(s): Horie M, Miyashita N, Mikami Y, Noguchi S, Yamauchi Y, Suzukawa M, Fukami T, Ohta K, Asano Y, Sato S, Yamaguchi Y, Ohshima M, Suzuki HI, Saito A, Nagase T.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. Volume: 314 Issue: 1 Pages: L177-L191
  • DOI: 10.1152/ajplung.00193.2017
  • Peer Reviewed / Open Access
• [Journal Article] Antibody therapy for the management of severe asthma with eosinophilic inflammation (2017)
  • Author(s): Ohta Ken、Nagase Hiroyuki、Suzukawa Maho、Ohta Shin
  • Journal Title: International Immunology Volume: 29 Issue: 7 Pages: 337-343
  • DOI: 10.1093/intimm/dxx045
  • Peer Reviewed
• [Presentation] IgAによる肺線維芽細胞の活性化 (2019)
  • Author(s): 鈴川真穂
  • Organizer: 第６８回日本アレルギー学会学術大会
• [Presentation] 結核感染におけるQFT Gold Plus (QFT-Plus), ＱFT Gold In Tube（QFT-3G）中サイトカイン値の比較検討 (2019)
  • Author(s): 鈴川真穂
  • Organizer: 第93回日本感染症学会総会・学術講演会
• [Presentation] ABPMにおける気道粘膜局所でのIgE産生の検討 (2019)
  • Author(s): 鈴川真穂
  • Organizer: 第63回日本医真菌学会総会・学術集会
• [Presentation] Pathogenic activity of secretory IgA in lung fibrosis (2018)
  • Author(s): 鈴川 真穂
  • Organizer: The 47th Japanese Society of Immunology
• [Presentation] 結核感染におけるQFT Gold Plus, QFT Gold In Tubeの残血漿中サイトカイン値の検討 (2018)
  • Author(s): 鈴川 真穂
  • Organizer: 第67回日本感染症学会東日本地方会学術集会・第65回日本化学療法学会東日本支部総会合同学会2018
• [Presentation] Baseline serum cytokine levels may predict responders to omalizumab and mepolizumab (2018)
  • Author(s): 鈴川 真穂
  • Organizer: XXIV World Congress of Asthma
  • Int'l Joint Research
• [Presentation] メポリズマブ投与喘息患者における血清サイトカイン値の検討 (2018)
  • Author(s): 鈴川 真穂
  • Organizer: 第６７回日本アレルギー学会学術大会
• [Presentation] 間質性肺炎の肺病変におけるIL-9およびIL-9レセプターの発現解析 (2018)
  • Author(s): 鈴川 真穂
  • Organizer: 第５８回日本呼吸器学会学術講演会
• [Presentation] 血中サイトカインを用いたオマリズマブの治療効果予測因子の検討 (2017)
  • Author(s): 鈴川真穂
  • Organizer: 第66回 日本アレルギー学会学術大会
• [Book] 医薬ジャーナル (0287-4741)54巻11号 【喘息治療における分子標的治療】 基礎総論 喘息における気道炎症の概説(解説/特集) (2018)
  • Author(s): 鈴川 真穂
  • Total Pages: 5
  • Publisher: 医薬ジャーナル社
• [Book] 日本呼吸器学会誌 (2186-5876)7巻4号 成人における4価インフルエンザ不活化スプリットワクチンの免疫原性と安全性の検討 (2018)
  • Author(s): 渡邉 直昭(国立病院機構東京病院 呼吸器センター), 大島 信治, 永井 英明, 加藤 貴史, 齋藤 美奈子, 五十嵐 彩夏, 鈴川 真穂, 川島 正裕, 浅里 功, 松井 弘稔
  • Total Pages: 7
  • Publisher: (一社)日本呼吸器学会
• [Book] アレルギーの臨床 (0285-6379)38巻2号 アレルギー療養に対する肥満の影響 (2018)
  • Author(s): 鈴川 真穂
  • Total Pages: 4
  • Publisher: (株)北隆館