Neutrophil RNA-binding proteins in inflammatory kidney diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08222
• 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: The University of Tokyo
• Principal Investigator: Nishi Hiroshi 東京大学, 医学部附属病院, 准教授 (90784174)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 好中球 / 腎 / 白血球 / 炎症 / 腎臓 / 血管生物学

Outline of Final Research Achievements

During the acute and active phases of inflammatory kidney disease, multiple RNA sensors and kinases were activated (autophosphorylation) by opsonization of foreign microorganisms and IgG, which is assumed to be an immune complex. Activation of these kinases ultimately contributes to the cell biological properties of neutrophils, such as respiratory burst, degranulation, extracellular DNA trapping, and transmigration. These have aggressive aspects not only against foreign microorganisms but also against self-tissues, which may explain the molecular basis of autoimmune diseases that originate from immune complexes.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

炎症刺激によって好中球内の RNA センサー兼リン酸化酵素が活性化（自己リン酸化）されることがわかった．また，その下流に既報で知られるリン酸化カスケードが存在を確認したほか，リン酸化アレイにより新規のリン酸化酵素を従えることも明らかにした．これらは自己組織に対して攻撃的な細胞活性化に寄与することから，免疫複合体を起点とする自己免疫疾患の創薬標的ともなりえる．