Establishment of novel biomarker for detection of tertiary lymphoid tissue

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16081
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: Sato Yuki 京都大学, 医学研究科, 特定助教 (60762086)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 三次リンパ組織 / 慢性腎臓病 / 急性腎障害 / 慢性炎症

Outline of Final Research Achievements

Unlike reversible acute kidney injury (AKI) in the young, AKI in the elderly often leads to end-stage renal diseases, yet the mechanism of incomplete repair was unclear. In the previous study, we found that aged mice, but not young mice, developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI, which generate, sustain and even enforce aberrant inflammation, resulting in maladaptive repair. TLTs were also detected in human aged kidneys and kidneys with other diseases, yet the clinical relevance remains unclear because of the lack of methodology for their evaluation.
Here, we established the phenotypic evaluation method of TLT based on the presumed developmental stages and showed the potential of TLT stage as a histological marker reflecting local injury and inflammation in murine and human kidney. TLT staging strategy may be effective in assessing disease activity and efficacy of therapy, and thus potentially improve our assessment of CKD patients.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

三次リンパ組織の成熟度に応じた多様性が存在することを明らかにし、その三次リンパ組織の成熟度に応じて三次リンパ組織の新規組織分類を確立した。本分類を用いて、ヒトおよびマウスの三次リンパ組織は腎臓の組織障害度を反映する新規腎障害組織マーカーとなること、治療介入により可逆性を示すことをを明らかにしました。今回三次リンパ組織を軸とした新たな腎臓病の評価系を確立したことによって、様々な腎臓病の病態解明につながり、重症度評価・治療法の選定などを含めた腎臓病の日常診療が前進することが期待されます。