Involvement of IL-17 cytokine family in protective immunity to pulmonary mycobacterial infection.
| Project/Area Number |
15K08468
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
UMEMURA Masayuki 琉球大学, 熱帯生物圏研究センター, 准教授 (90359985)
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| Co-Investigator(Kenkyū-buntansha) |
松崎 吾朗 琉球大学, 熱帯生物圏研究センター, 教授 (30229455)
福井 雅之 青森大学, 薬学部, 准教授 (60392502)
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| Research Collaborator |
FUKUI Masayuki 青森大学, 薬学部, 准教授 (60392502)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 結核 / IL-17A / IL-17F / 肺 / 結核菌 / IL-17 / γδ T細胞 / Th17細胞 / ILC3 / マイコバクテリア / 肉芽腫 |
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| Outline of Final Research Achievements |
Although interleukin (IL)-17A is known to play an important role in protective immunity against lung mycobacterial infection, the role of IL-17F, a cytokine with high homology to IL-17A, is unclear. We demonstrate that the protective response to pulmonary Mycobacterium tuberculosis infection is impaired in IL-17F knockout (KO) mice at the early stage but not in the chronic stage of the infection. IL-17F-producing cells were detected in neither T cells nor non-T lymphoid cells in the infected lung. In contrast, the type II alveolar epithelial cell (AEC) line expressed IL-17F, and its expression was upregulated by mycobacterial infection in vitro. The production of IL-17F was also detected in the pulmonary epithelial cells in the lung of wild-type (WT) mice infected with M. tuberculosis. Thus, IL-17F produced by AEC has an important role in protective immunity against M. tuberculosis infection in the early stage but not in the chronic stage of infection.
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| Academic Significance and Societal Importance of the Research Achievements |
結核は20 世紀最大の恐怖を与えた慢性持続感染症であり、依然として猛威を奮い続けている。現在実用化されている唯一の結核ワクチンであるBCG は小児における播種性結核にはある程度の予防効果が認められているものの、成人肺結核に対しての予防効果は極めて低い。本研究では、IL-17ファミリーを中心としたサイトカイン・ネットワークを解析したことにより、結核制御に最も重要なIFN-γを主体とする1型免疫応答に対する協調的作用や相互制御を十分に理解することができた。本研究成果は、肺結核に対して有効性の高い新規ワクチン戦略の開発ならびに結核菌の排除に有効な革新的治療方法の開発につながると思われる。
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Report
(5 results)
Research Products
(46 results)
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[Journal Article] C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol Mannosides to Promote a Th1 Response during Infection2016
Author(s)
Toyonaga K, Torigoe S, Motomura Y, Kamichi T, Hayashi JM, Morita YS, Noguchi N, Chuma Y, Kiyohara H, Matsuo K, Tanaka H, Nakagawa Y, Sakuma T, Ohmuraya M, Yamamoto T, Umemura M, Matsuzaki G, Yoshikai Y, Yano I, Miyamoto T, Yamasaki S.
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Journal Title
Immunity
Volume: 45
Issue: 6
Pages: 1245-1257
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2(+)Vγ6(+)γδ T cells.2015
Author(s)
Akitsu A, Ishigame H, Kakuta S, Chung SH, Ikeda S, Shimizu K, Kubo S, Liu Y, Umemura M, Matsuzaki G, Yoshikai Y, Saijo S, Iwakura Y.
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Journal Title
Nat Commun
Volume: 6
Issue: 1
Pages: 7464-7464
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] The function of a DAP12-associated receptor recognizing mycobacterial lipids2018
Author(s)
Iizasa E., Uematsu T., Kiyohara H., Chuma Y., Kutobta M., Umemura M, Matsuzaki G, Yamasaki S., Yoshida H., Hara H.
Organizer
The 52nd U.S.-Japan Cooperative Medical Sciences Program, Mycobacteria Panel Meeting
Related Report
Int'l Joint Research / Invited
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[Presentation] Role of IL-33 on innate immunity in pulmonary mycobacterial infection.2015
Author(s)
Fukui, M., Fukui, C., Nakae, S., Matsuzaki, G., Umemura, M.
Organizer
第44回日本免疫学会学術集会
Place of Presentation
札幌コンベンションセンター, 北海道札幌市
Year and Date
2015-11-18
Related Report
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[Presentation] Role of IL-33 in chronic pulmonary mycobacterial infection.2015
Author(s)
Umemura, M., Fukui, M., Yamasaki, M., Fukui, C., Nakae, S., Matsuzaki, G.
Organizer
IMMUNOLOGY 2015TM AAI Annual Meeting
Place of Presentation
Ernest N. Morial Convention Center, New Orleans, Louisiana, USA
Year and Date
2015-05-08
Related Report
Int'l Joint Research
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