| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Regulatory B cells (Breg) are involved in the pathogenesis of inflammatory bowel diseases. We investigated the molecular mechanisms how resident bacteria induce IL-10-producing Breg and ameliorate mucosal inflammation using several Toll-like receptor (TLR) knockout (KO) mice. B cells from TLR2 KO, but not TLR4 KO or TLR9 KO, mice produced low IL-10 in the presence of bacterial stimulation and failed to ameliorate T cell-mediated colitis. Next, we sought to determine the TLR2-dependent IL-10 production by microbiota-activated B cells. Western blotting indicated that a PI3K-AKT-GSK3B pathway is activated in the presence of TLR2 but not TLR4 stimulation. PI3Kp110d KO B cells were neither produce sufficient IL-10 when stimulated with bacteria nor ameliorated mucosal inflammation in vivo. These findings increase our understanding of the pathogenesis of IBD and regulation of mucosal homeostasis by resident microbiota.
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