Analysis of T cell-derived proteoglycans in tissue inflammation and fibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08769
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Chiba University
• Principal Investigator: Iwamura Chiaki 千葉大学, 大学院医学研究院, 特任講師 (10513062)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: プロテオグリカン / セルグリシン / COVID-19 / 炎症性肺疾患

Outline of Final Research Achievements

To examine the role of Serglycin in inflammatory responses, which is a proteoglycan, we generated Serglycin knockout (KO) mice. Inflammatory responses, such as allergic airway inflammation, were attenuated in Serglycin KO mice as compared to wild type mice, indicating that Serglycin is important for induction of inflammatory responses. However, CD4+ T cell specific Serglycin KO mice did not show the reduction of airway inflammation, suggesting that Serglyin released by another immune cell is involved in the induction of inflammation. The high expressions of Serglycin were observed in the infiltrating cells of nasal polyps taken from the patients with eosinophilic sinusitis and in the peripheral blood mononuclear cells of patients with severe COVID-19. Thus, Serglycin is involved in human inflammatory diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

アレルギー性疾患や自己免疫疾患などの慢性炎症性疾患は、その根治が難しく、また炎症が遷延化するほど、組織線維化などの臓器の機能障害を引き起こすことがある。炎症を引き起こす機序として、これまで様々な炎症性細胞やそれらが産生するサイトカインについて解析がなされてきた。本研究では炎症性細胞が出すプロテオグリカン（セルグリシン）が炎症の誘導に関与することを明らかにしている。すなわち、慢性炎症性疾患に対し、これまでとは異なる治療アプローチの開発に寄与する可能性があり、本研究成果は社会的な意義があると考えられる。