Direct involvement of HTLV-1 for pathogenesis of Sjogren's syndrome

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08884
• 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: Nihon University (2021); Nagasaki University (2019-2020)
• Principal Investigator: NAKAMURA Hideki 日本大学, 医学部, 教授 (10437832)
• Co-Investigator(Kenkyū-buntansha): 清水 俊匡 長崎大学, 病院(医学系), 助教 (40770467) ; 川上 純 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639) ; 高谷 亜由子 長崎大学, 病院(医学系), 医員 (90821380)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: シェーグレン症候群 / HTLV-1 / 濾胞性樹状細胞

Outline of Final Research Achievements

It has been suggested that Sjogren's syndrome (SS) is associated with human T-cell leukemia virus type 1 (HTLV-1). The action of follicular dendritic cells (FDCs) and B cells induces autoantibody producing plasma cell differentiation, but secondary follicular formation in the salivary glands of the patients with HTLV-1-associated myelopathy is inhibited, and the effect of HTLV-1 on FDCs was investigated. Co-culture with HCT-5/MT-2 suppressed the expression of CXCL13 and BAFF. BAFF showed a decreasing tendency when HCT-5/MT-2 was added to FDC-like cells. BAFF / CXCL13 concentrations tended to be lower in anti-HTLV-1 antibody-positive SS than in antibody-negative SS. It was suggested that the low frequency of anti-Ro / SS-A antibody appearance in anti-HTLV-1 antibody-positive SS may be due to functional suppression of FDC-like cells.

Free Research Field

リウマチ・膠原病

Academic Significance and Societal Importance of the Research Achievements

シェーグレン症候群（以下SS）における自己抗体産生系の中で、異所性二次濾胞内上流に位置すると思われる濾胞性樹状細胞（FDC）様細胞のはたらきが、HTLV-1感染細胞HCT-5/MT-2による直接作用によって阻害され、少なくとも細胞内のCXCL13/BAFF発現とインターフェロン刺激で増加するBAFF分泌が抑制されている結果が得られた。また、抗HTLV-1抗体陽性SS患者血清中のBAFF/CXCL13濃度は抗体陰性SS患者より低い傾向が示された。以上より抗HTLV-1抗体陽性SSにおける抗Ro/SS-A抗体出現頻度の低さが、FDC様細胞の機能抑制によって生じている可能性が示唆された。