Analysis of transition from inflammation to regeneration of myeloide cell regulated soluble Siglec-9 and MCP-1

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15720
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: The University of Tokushima
• Principal Investigator: HASHIMOTO Noboru 徳島大学, 大学院医歯薬学研究部(歯学域), 助教 (90712365)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Siglec-9 / 炎症 / 免疫 / 組織修復 / マクロファージ

Outline of Final Research Achievements

Macrophages are divided to M1 macrophages involved in pro-inflammation and M2 macrophages involved in the anti-inflammation and tissue repair. An imbalance of M1/M2 polarization associates with homeostatic disruption and disease. We have reported that monocyte-attracting chemokine MCP-1 and soluble sialic acid-binding immunoglobulin-type lectin (sSiglec)-9 were identified as novel inducers for M2-polarization and their combination repairs several inflammation states of animal models. In this research, sSiglec-9 reduced inflammatory cytokine production in various type of mouse and human macrophages stimulated by IFN gamma and LPS. The combination of sSiglec-9 and MCP-1 ameliorated bleomycin-induced lung fibrosis and D-galactosamine-induced acute liver failure. sSiglec-9 ameliorated ovalbumin-induced atopic dermatitis. We analyzed sSiglec-9 targeting molecules using liquid chromatography-mass spectrometry and identified 606 proteins as candidates of sSiglec-9 binding target.

Free Research Field

免疫学、糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

間質性肺炎、劇症肝炎、アトピー性皮膚炎など炎症性疾患に対する治療薬はその炎症抑制効果を狙ったものが多く、組織の再生効果を狙ったものはない。本研究では乳歯歯髄幹細胞が分泌する抗炎症組織再生効果を示す分子sSiglec-9とMCP-1に注目し、その効果と標的分子の同定を目指した。これらの詳細なメカニズムが明らかになれば、抗炎症による症状緩和だけでなく組織を修復再生させる画期的な治療法の基盤になることが期待される。