Analysis of multiple defense mechanisms of "type 3 immune response" in mycobacteria infected lungs
| Project/Area Number |
18K07117
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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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| Review Section |
Basic Section 49050:Bacteriology-related
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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)
高江洲 義一 琉球大学, 熱帯生物圏研究センター, 准教授 (60403995)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | interleukin-17 / TCR γδ T細胞 / 結核 / 肺 / interleukin-1β / interleukin-23 / 結核菌 / TcR γδT細胞 / IL-17 / 3型免疫応答 / IL-23 / IL-1β / IL-17A / γδ T細胞 / 肉芽腫 |
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| Outline of Final Research Achievements |
We examined which mechanisms of γδ T cells induce mycobacteria antigen (PPD)-specific IL-17A production. In transwell culture with γδ T cells and antigen presenting cells (APC) plus PPD, IL-17A-producing γδ T (γδT17) cells showed increased IL-17A production, and similar results were obtained in experiments with APCs derived from IL-23p19 KO mice. When IL-1β and IL-23 were neutralized, the enhancement of IL-17A production was remarkably reduced. When PPD was directly added to the infected lymphocytes without APC, IL-17A production of γδT17 cells increased. These results suggest that the IL-1β but not IL-23 is essential in IL-17A production by γδT17 cells. On the contrary, enhancement of γδT17 cells was also observed in a system in which PPD stimulation was directly applied to lung lymphocytes. This suggests that suggest that recognition of PPD by T cell receptor or pattern recognition receptors is also important in IL-17A production of γδT17 cells.
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| Academic Significance and Societal Importance of the Research Achievements |
医学ならびに医療技術の発展により不治の病とされてきた結核も人為的制御可能な疾患になりつつある。しかし、現在唯一実用化されている結核ワクチンであるBCGは、小児結核の発病予防には高い効果が認められているものの、成人に対しての予防効果は極めて低い。また、結核菌は結核菌特異的な獲得免疫応答の誘導を何らかの機序で遅延させるが、その現象はBCGを接種しても回避できない。本研究で得られた成果はこれまでのIFN-γ産生を主体とした細胞性免疫を増強させるというワクチン開発のドグマから脱け出す新たな発想を生むための非常に重要な基盤研究である。
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Report
(5 results)
Research Products
(41 results)
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[Journal Article] GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation.2022
Author(s)
Kurane, T., Matsunaga, T., Ida, T., Sawada, K., Nishimura, A., Fukui, M., Umemura, M., Nakayama, M., Ohara, N., Matsumoto, S., Akaike, T., Matsuzaki, G., Takaesu, G.
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Journal Title
FASEB Journal
Volume: 36
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.2021
Author(s)
Iizasa, E., Chuma, Y., Uematsu, T., Kubota, M., Kawaguchi, H., Umemura, M., Toyonaga, K., Kiyohara, H., Yano, I., Colonna, M., Sugita, M., Matsuzaki, G., Yamasaki, S., Yoshida, H., Hara, H.
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 2299-2314
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Porphyromonas gingivalis components/secretions synergistically enhance pneumonia caused by Streptococcus pneumoniae in mice.2021
Author(s)
Okabe, T., Kamiya, Y., Kikuchi, T., Goto, H., Umemura, M., Suzuki, Y., Sugita, Y., Naiki, Y., Hasegawa, Y., Hayashi, J., Kawamura, S., Sawada, N., Takayanagi, Y., Fujimura, T., Higuchi, N., Mitani, A.
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Journal Title
Int. J. Mol. Sci.
Volume: 22
Issue: 23
Pages: 12704-12715
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] TREM2は非糖鎖付加ミコール酸を認識し、マクロファージの抗抗酸菌免疫応答を抑制する2021
Author(s)
飯笹英一, 中馬康志, 植松崇之, 久保田未央, 川口博明, 梅村正幸, 豊永憲司, 清原秀泰, 矢野郁也, Marco Colonna, 杉田昌彦, 松崎吾朗, 山崎晶, 吉田裕樹, 原博満
Organizer
第85回日本インターフェロン・サイトカイン学会学術集会
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