2021 Fiscal Year Final Research Report

Analysis of multiple defense mechanisms of "type 3 immune response" in mycobacteria infected lungs

Research Project

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Project/Area Number	18K07117
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 49050:Bacteriology-related
Research Institution	University of the Ryukyus
Principal Investigator	Umemura Masayuki 琉球大学, 熱帯生物圏研究センター, 准教授 (90359985)
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)
Project Period (FY)	2018-04-01 – 2022-03-31
Keywords	interleukin-17 / TCR γδ T細胞 / 結核 / 肺
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.
Free Research Field	感染免疫
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。