Investigation of the pathogenic mechanism of Sjogren's syndrome based on intracellular metabolism and establishment of novel therapeutic strategies

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K19759
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Oral Science and related fields
• Research Institution: Nihon University (2020-2022); The University of Tokushima (2017-2019)
• Principal Investigator: YAMAMOTO Akiko (山田安希子) 日本大学, 歯学部, 助教 (70452646)
• Project Period (FY): 2017-06-30 – 2023-03-31
• Keywords: 自己免疫疾患 / シェーグレン症候群 / T細胞

Outline of Final Research Achievements

In Sjogren's syndrome, there is a marked lymphocytic infiltrate around the lacrimal and salivary glands. Most of these lymphocytes are activated autoreactive T cells, and the exocrine function of the lacrimal and salivary glands is damaged by these activated autoreactive T cells. However, the mechanism regulating the activation of autoreactive T cells is still unknown.
Therefore, we performed a quantitative proteomic analysis of T cells isolated from lymphoid organs of both Sjogren's syndrome model mice and normal mice, and selected a molecule suggested to be associated with the pathogenesis of Sjogren's syndrome and generated a gene knockout mouse for this molecule.

Free Research Field

口腔病理学

Academic Significance and Societal Importance of the Research Achievements

本法におけるシェーグレン症候群の患者総数は約10万人と推定されている。これまで種々の研究が行われてきたにもかかわらず、治療法は乾燥症状に対する対症療法のみで根本的治療法はまだ開発されていない。本研究では、涙腺および唾液腺を傷害する主な免疫細胞であるT細胞を対象とした定量的プロテオミクス解析を実施し、病態の増悪と相関する発現変動を示す分子を同定した。当該分子がシェーグレン症候群の有効な治療標的分子となり得る可能性は高く、臨床的波及効果は高いと考えられる。