Investigation of the pathogenesis of Sjogren's syndrome based on single-cell RNA sequencing

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18479
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: The University of Tokushima
• Principal Investigator: OTSUKA Kunihiro 徳島大学, ポストLEDフォトニクス研究所, 助教 (90847865)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: シェーグレン症候群 / 自己免疫疾患 / CD4陽性T細胞 / 唾液腺

Outline of Final Research Achievements

Sjogren’s syndrome (SS) is an autoimmune disease affected salivary and lacrimal glands. We made a mouse model for SS (SS model), and performed single cell RNA-sequencing by using salivary glands from SS model and control mice. As a result, a unique CD4+ T cell population that expressed several proinflammatory molecules was found in salivary glands from SS model, but not control. The treatment with a neutralizing antibody improved the autoimmune pathology in SS model. The expression of a receptor for a proinflammatory molecule also was increased in salivary glands from SS model, suggested that a proinflammatory signal via a unique CD4+ T cell population might contribute to the pathogenesis for SS. This study is expected that a unknown mechanism for the development of SS will be clarified and new strategies for the diagnosis or treatment for SS will be found.

Free Research Field

免疫病理学

Academic Significance and Societal Importance of the Research Achievements

我々が見出したSS特異的なCD4陽性T細胞は、SS病態でどのように関与しているかについて、これまでに報告がない。そのため、新規の診断マーカーや治療標的の確立のために非常に重要な細胞集団であると推察される。また、我々の想定している発症機序は、唾液腺局所で生じる現象であり、この機序を阻害することは全身的な影響を最小限にしながら、SSの発症を抑制できるため、低侵襲な治療法の開発が期待される。