| 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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| 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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