Mast cells can produce transforming growth factor b1 and promote tissue fibrosis during the development of Sjogren's syndrome-related sialadenitis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08898
• 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: Kurume University
• Principal Investigator: Kaieda Shinjiro 久留米大学, 医学部, 准教授 (20330798)
• Co-Investigator(Kenkyū-buntansha): 星野 友昭 久留米大学, 医学部, 教授 (00261066)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: シェーグレン症候群 / マスト細胞 / 唾液腺炎 / 組織線維化 / TGFβ

Outline of Final Research Achievements

This study investigated the associations of mast cells with immune-mediated inflammation and fibrosis in patients with primary　Sjogren’s syndrome (pSS). Mast cell numbers in labial salivary glands were significantly greater in pSS than in control individuals. In salivary glands from patients with pSS, mast cell number was significantly correlated with fibrosis extent; moreover, mast cells were located　near fibrous tissue and expressed TGFβ1. Col1a and TGFβ1 mRNAs were upregulated in cocultured fibroblasts and HMC-1 cells, respectively. Fibroblasts cultured in HMC-1 conditioned medium exhibited upregulation of Col1a mRNA; this was abrogated by TGFβ1 neutralizing antibodies.　 Mast cell numbers were elevated in patients with pSS-related sialadenitis; these cells were located near fibroblasts and expressed TGFβ1. TGFβ1 could induce collagen synthesis in fibroblasts, which might contribute to fibrosis.

Free Research Field

リウマチ膠原病内科

Academic Significance and Societal Importance of the Research Achievements

シェーグレン症候群は唾液や涙液分泌が障害され慢性的に乾燥症状が持続し、QOLが低下する難治性疾患である。唾液腺炎症を抑制する根本治療は確立されておらず対症療法が主となっている。本研究ではマスト細胞が唾液腺炎症部位で増殖し、TGFβ1を産生を介して線維芽細胞によるコラーゲン線維産生を促進することを明らかにした。シェーグレン症候群においてマスト細胞およびTGFβ1を阻害することで組織線維化を抑制し唾液分泌能低下を軽減させる新規治療法の確立が期待される。