Rictor Ameliorates Acute Antibody-Mediated Rejection Following Kidney Transplantation by Suppressing Macrophage M1 Polarization Through p65-NLRP3 Axis

IF 14.1 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Advanced Science Pub Date : 2025-06-20 DOI:10.1002/advs.202417119

Bin Ni, Chengcheng Yang, Junqi Zhang, Zhou Hang, Ming Zheng, Dengyuan Feng, Qinghuan Shen, Jinxu Miao, Xulin Sun, Li Sun, Baixin Shen, Min Gu, Zijie Wang

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Abstract

Antibody-mediated rejection (ABMR) represents the leading cause of kidney allograft failure over a long term after transplantation. Early infiltration of macrophages predicts the adverse outcome of grafts, yet the underlying mechanisms remain to be elucidated. Significant infiltration of M1 macrophages and upregulation of Rictor in macrophages are observed in ABMR allografts. Deficiency of Rictor in macrophages exacerbates histological injury and shortens the survival of ABMR allografts by promoting macrophage M1 polarization. Additionally, loss of Rictor in primary bone marrow-derived macrophages facilitates NLRP3 inflammasome activation through activating NF-κB. Mechanistically, Rictor upregulates E3 ubiquitin ligase SOCS1 to enhance K48-linked ubiquitination of p65, thereby suppressing macrophage M1 polarization. Taken together, Rictor ameliorates acute ABMR following kidney transplantation by suppressing macrophage M1 polarization through the p65-NLRP3 axis and may serve as a therapeutic target for ABMR.

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Rictor通过p65-NLRP3轴抑制巨噬细胞M1极化，改善肾移植后急性抗体介导的排斥反应

抗体介导的排斥反应（ABMR）是移植后长期发生同种异体肾移植失败的主要原因。巨噬细胞的早期浸润预示着移植物的不良后果，但其潜在的机制仍有待阐明。同种异体ABMR移植中M1巨噬细胞明显浸润，巨噬细胞中Rictor表达上调。巨噬细胞中缺乏Rictor通过促进巨噬细胞M1极化，加重ABMR同种异体移植物的组织学损伤，缩短其存活时间。此外，原代骨髓源性巨噬细胞中Rictor的缺失通过激活NF-κB促进NLRP3炎性体的激活。机制上，Rictor上调E3泛素连接酶SOCS1，增强k48相关的p65泛素化，从而抑制巨噬细胞M1极化。综上所述，Rictor通过p65-NLRP3轴抑制巨噬细胞M1极化，改善肾移植后急性ABMR，可能作为ABMR的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY

CiteScore

18.90

自引率

2.60%

发文量

1602

审稿时长

1.9 months

期刊介绍： Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.