Mechanism of kidney injury associated with graft-versus-host disease after allogenic stem cell transplantation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08410
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Yamagata University
• Principal Investigator: Ichikawa Kazunobu 山形大学, 医学部, 講師 (50436218)
• Co-Investigator(Kenkyū-buntansha): 東梅 友美 山形大学, 医学部, 講師 (40802111)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 造血幹細胞移植 / 急性移植片対宿主病 / 急性腎障害 / allo-HCT / aGVHD / AKI / エラフィン / elafin

Outline of Final Research Achievements

We investigated whether allogeneic donor T cells target kidney in murine models of aGVHD. Donor MHC-positive cells were present in the renal pathology specimens from allogeneic mice. The characteristics of these donor-derived T cells were analyzed using flow cytometry. Both CD4+ and CD8+ cells were increased in allogeneic animals and these T cells demonstrated elevated surface markers of activation and exhaustion as well as secretion of proinflammatory cytokines and cytotoxic proteins. Examination of protein expression in renal tissue showed an increase of neutrophil gelatinase-binding lipocalin (NGAL) and elafin in allogeneic recipients. In an in vitro cytotoxic T lymphocyte (CTL) assay, co-culture with alloreactive T cells increased apoptosis of renal cells. Our study demonstrated that immune responses induced by donor T cells are involved in renal cell injury in recipients, suggesting that the kidney is also an aGVHD target organ.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

造血細胞移植の合併症として急性腎障害（AKI）がしばしば発生し、その原因として薬剤や感染症などの要因が想定されているが詳細には解明されていなかった。本研究では、同種ドナー由来のTリンパ球がレシピエントの腎臓を傷害していること、すなわちGVHDが造血細胞移植後のAKIに寄与していること実験系で示した。造血細胞移植患者の腎予後を改善するために、腎臓特異的GVHDのより詳細な病態解明と治療法の開発が望まれる。