A study of microbiota activated regulatory B cells in inflammatory bowel diseases.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09382
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Shimane University
• Principal Investigator: Mishima Yoshiyuki 島根大学, 学術研究院医学・看護学系, 助教 (30397864)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 腸内細菌 / 炎症性腸疾患 / 制御性免疫細胞 / 粘膜免疫 / Toll like receptor

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.

Free Research Field

炎症性腸疾患

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、IBDの病態における腸内細菌を介したBreg誘導機構の一端を解明できたと考える。このシステムを応用し、生体内で効率的にBreg誘導ができるようになれば、安全で有効性のたかい新規のIBD治療法開発につながる可能性がある。難渋している現行のIBD治療とは異なるアプローチであり、実用化されれば臨床的意義は大きいと考える。