Analysis of the molecular basis of tertiary lymphoid tissue formation that results in age-related kidney vulnerability

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04187
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: Yanagita Motoko 京都大学, 医学研究科, 教授 (70378769)
• Co-Investigator(Kenkyū-buntansha): 河本 宏 京都大学, ウイルス・再生医科学研究所, 教授 (00343228)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 炎症 / 加齢

Outline of Final Research Achievements

Previously we found that tertiary lymphoid tissues are formed in the aged kidney after renal injury, and cause prolonged inflammation and delayed regeneration (JCI Insight 2016). Tertiary lymphoid tissues are the structures similar to lymph nodes, and are formed in non-lymphoid tissues after chronic inflammation. Tertiary lymphoid tissues amplify the immune response through the interaction and proliferation of T cells and B cells. More recently, we have found that tertiary lymphoid tissue reflects tissue damage and inflammation (Kidney Int in press). In this study, we addressed the question, "Why does tertiary lymphoid tissue form in the aged kidney?" and identified the cells responsible for age-related tertiary lymphoid tissue formation.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

三次リンパ組織に対する治療介入が腎修復を促進する点、高齢ヒト腎でも三次リンパ組織が観察される点から、三次リンパ組織は治療標的として有望である。本研究で三次リンパ組織形成機構が解明できれば、治療薬開発に結びつく可能性が高く、種々の腎臓病モデルで観察できていることから、このような薬剤は高齢者腎臓病に対して広範な有効性が期待できる。「加齢に伴う臓器障害応答性の変容」は普遍的な現象であり、その共通メカニズムとして三次リンパ組織形成を提案することができれば、生物学における意義も大きい。