Cross-talk between Th cells and inflammatory macrophages in chronic inflammatory respiratory diseases
| Project/Area Number |
26461178
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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 |
Respiratory organ internal medicine
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
石井 幸雄 筑波大学, 医学医療系, 教授 (80272194)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Th1 / Th17 / T-bet / RORγt / 肺胞蛋白症 / 非結核性抗酸菌 / 非結核性抗酸菌症 / Th1細胞 / Th17細胞 / マクロファージ |
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| Outline of Final Research Achievements |
Overexpression of T-bet, a master transcription factor in Th1 cells, induced pulmonary alveolar proteinosis (PAP)-like disease in T-bet-transgenic mice (T-bet-tg). T-bet-tg alveoli with PAP phenotype showed remarkable reorganization of alveolar mononuclear phagocyte subpopulations and impaired function, in addition to augmented T-cell infiltration. PAP development in T-bet-tg was also found to be associated with increased migration of myeloid cells from the bone marrow into the peripheral blood.
We next investigated the role of Th1/Th17 balance in host responses against Mycobacterium avium complex (MAC) infection. Neutrophilic pulmonary inflammation following MAC infection was enhanced in T-bet-deficient mice and in mice overexpressing RORγt, a master regulator for Th17 cell development.
Our results suggest that imbalance of Th lineage-specific master regulatory transcription factors may be critical determinants for the development of PAP and host resistance to MAC infection.
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Report
(4 results)
Research Products
(4 results)
