Research on the Tonsil Immune Diversity Involved in the development of IgA Nephropathy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Niigata University
• Principal Investigator: Goto Shin 新潟大学, 医歯学系, 准教授 (00463969)
• Co-Investigator(Kenkyū-buntansha): 成田 一衛 新潟大学, 医歯学系, 教授 (20272817)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: IgA腎症 / 扁桃 / 1細胞RNA-Seq / T細胞受容体レパトア

Outline of Final Research Achievements

In this study, we planned to use excised tonsils to elucidate the details of the immune response in IgA nephropathy (IgAN). Both bulk RNA-Seq and single-cell nucleus RNA-Seq of tonsil tissue revealed an up-regulation of epithelial-related gene expression in IgAN patients compared to chronic tonsillitis patients. In terms of cell-cell interactions, interactions between epithelial gene groups and immune cells, including dendritic cells, were detected. Regarding the tonsil T-cell receptor (TCR) repertoire, IgAN patients showed significantly lower similarity in the TCR repertoire alpha chain compared to chronic tonsillitis patients, with differences in shared clones. Features of the CDR3 sequences of these shared clones and their association with tonsil APRIL and IgA-binding bacteria were observed.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

本研究からIgA腎症患者の粘膜免疫異常について、特に扁桃組織において遺伝子発現プロフィールが明らかになった。国内ではIgA腎症に対する治療として扁桃摘出術およびステロイド治療が広く行われている。扁桃摘出の理論的根拠として、また扁桃解析をIgA腎症の粘膜免疫異常のモデル解析として研究を進めることは実際の臨床診療にフィードバックする点で意義があると思われる。今後、新たな治療ターゲットの解明につながることが期待される。