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
{"title":"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","authors":"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","doi":"10.1002/advs.202417119","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":"12 34","pages":""},"PeriodicalIF":14.1000,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442627/pdf/","citationCount":"0","resultStr":"{\"title\":\"Rictor Ameliorates Acute Antibody-Mediated Rejection Following Kidney Transplantation by Suppressing Macrophage M1 Polarization Through p65-NLRP3 Axis\",\"authors\":\"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\",\"doi\":\"10.1002/advs.202417119\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":117,\"journal\":{\"name\":\"Advanced Science\",\"volume\":\"12 34\",\"pages\":\"\"},\"PeriodicalIF\":14.1000,\"publicationDate\":\"2025-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442627/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced Science\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202417119\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202417119","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Rictor Ameliorates Acute Antibody-Mediated Rejection Following Kidney Transplantation by Suppressing Macrophage M1 Polarization Through p65-NLRP3 Axis
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
