Functional analysis of plasmacytoid dendritic cells regulated by lipid environmental responses

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24307
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0909:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Tohoku University
• Principal Investigator: Kobayashi Shuhei 東北大学, 医学系研究科, 助教 (90851345)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: FABP / pDC / Immune response

Outline of Final Research Achievements

We found that plasmacytoid dendritic cells (pDCs) express FABP5. FABP5 deficiency did not affect the distribution of pDCs in the spleen or lymph nodes. Furthermore, Toll-like receptor 7 (TLR7) and TLR9, which selectively express pDCs, were comparably expressed at steady state, but upon ligand stimulation, FABP5-deficient pDCs showed overexpression of inflammation-related genes. On the other hand, there was no significant difference in immunosuppression-related gene expression, suggesting that FABP5 may play a role in regulating the inflammatory balance of pDCs. They also found that increased expression of inflammation-related genes was caused by increased expression of the transcription factor IRF7 and increased phosphorylation of p 65, a component of NF-κB.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

pDCは炎症促進および抑制の機能を有する免疫応答の中枢を担う自然免疫細胞であり、様々な炎症性疾患の制御へ関与する。本研究から、pDCにおけるFABP5を介した脂質恒常性の維持が炎症制御に重要であることが明らかとなった。免疫細胞における脂質代謝変化の重要性が注目される中で、pDCにおける脂質代謝変化の影響を明らかにした報告はなく、pDCを介した免疫恒常性維持の理解や分子基盤の構築へ向けて大きな前進となった。今後、pDC内のFABP5による脂質恒常性が周辺細胞へどのような影響を及ぼすのか、細胞連関の観点から明らかにすると共に、in vivo実験から炎症性疾患の病態制御との関連性をより強固に示す。