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This study assessed how macrophage migration inhibitory factor (MIF)–mediated changes in the Th17/Treg ratio influence renal injury in CKD. Single-cell sequencing, flow cytometry, and a 5/6 nephrectomy mouse model were used to connect MIF levels to pathway activity, disease progression, and kidney function metrics, while AAV-MIF and ISO-1 tested causality and therapeutic potential.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mif-regulates-the-th17treg-ratio-to-exacerbate-kidney-injury-in-chronic-kidney-disease-research/441171/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/mif-regulates-the-th17treg-ratio-to-exacerbate-kidney-injury-in-chronic-kidney-disease-research/441171.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does MIF play in CKD according to this study?","Question",{"text":112,"@type":113},"MIF promotes the progression of CKD by regulating the Th17/Treg ratio, and it may serve as a potential therapeutic target to prevent CKD progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the researchers measure Th17/Treg changes in patients?",{"text":117,"@type":113},"Peripheral blood mononuclear cells were profiled using single-cell sequencing, and flow cytometry quantified CD4+ T cell subsets and MIF expression. 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This study aimed to investigate the impact of alterations in the Th17/Treg ratio mediated by the secretory protein macrophage migration inhibitory factor (MIF) on renal injury in CKD patients. Single-cell sequencing was performed on peripheral blood mononuclear cell (PBMC) from 15 CKD patients and 20 healthy individuals to compare the characteristics of T-cell subsets, followed by differential signaling pathway analysis. Peripheral blood samples from 20 CKD patients and 10 healthy donors were analyzed using flow cytometry to quantify CD4 + T cell subsets and MIF expression. A 5/6 nephrectomy mouse model and blood CD4 + T cells were extracted to verify the effects of MIF-related proteins on the Th17/Treg ratio and progression of CKD. Besides, AAV-MIF was locally administered into the renal tissue to achieve kidney-specific MIF suppression in CKD model. Single-cell sequencing revealed significant correlation between MIF levels and Th17/Treg ratios, identifying MIF-(CD74 + CXCR4) pathway involvement. Flow cytometry analysis of the clinical cohort demonstrated an elevated Th17/Treg ratio (p\u003C 0.01) in CKD patients compared to normal controls. MIF levels also correlated with renal parameters (Crea, p\u003C 0.001; BUN, p\u003C 0.0001; eGFR, p\u003C 0.0001) . In vitro experiments confirmed a significant increase (p\u003C 0.05) in Th17/Treg cells after MIF protein or serum from CKD patients, and these changes were partially reversed by an MIF inhibitor (ISO-1) (p\u003C 0.001) . Moreover, renal injury in CKD mice in the AAV-MIF group was significantly reversed. This study revealed that MIF promotes the progression of CKD by regulating the Th17/Treg ratio and that MIF serves as a potential target to prevent CKD.  \nRuijing Zhang and Keyi Fan contributed equally to this work and share the first authorcontributed equally to this work.  \n􀀍 Honglin Dong [honglindong@sxmu.edu.cn](honglindong@sxmu.edu.cn)  \n1 Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China  \n2 Vascular Institute of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi, China  \n3 Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China  \n1 3  \nGraphical Abstract  \nMIF regulates the Th17/Treg ratio to exacerbate kidney injury in chronic kidney disease  \nKeywords Chronic kidney disease (CKD) · Helper t cells (Th17) · Regulatory t cells (Tregs) · Macrophage migration inhibitory factor (MIF)  \nIntroduction  \nChronic kidney disease (CKD) is a noninfectious inflammatory state characterized by a long-term, progressive decline in renal function. Approximately 843.6 million people worldwide are affected by stage 1–5 CKD, according to the Global Prevalence of Chronic Kidney Disease 2019 study [1] . According to statistics provided by the WHO (2020), renal insufficiency is currently the seventh leading risk factor for death. CKD is a growing public health problem due to its increasing prevalence, resulting in premature deaths and significant pressure on global health funding for the treatment of advanced disease. Thus, elucidating the mechanisms underlying the progression of CKD is vital. The complex mechanisms by which C","cbCaic00O5V7nUZq","https://ap.wps.com/l/cbCaic00O5V7nUZq","pdf",12040508,15,"English","# Abstract\n# Introduction\n## CKD and its inflammatory mechanisms\n## MIF as an upstream proinflammatory mediator\n## Links between renal inflammation and T-cell subset differentiation","[{\"question\":\"What role does MIF play in CKD according to this study?\",\"answer\":\"MIF promotes the progression of CKD by regulating the Th17/Treg ratio, and it may serve as a potential therapeutic target to prevent CKD progression.\"},{\"question\":\"How did the researchers measure Th17/Treg changes in patients?\",\"answer\":\"Peripheral blood mononuclear cells were profiled using single-cell sequencing, and flow cytometry quantified CD4+ T cell subsets and MIF expression. The clinical cohort showed an elevated Th17/Treg ratio in CKD patients versus controls.\"},{\"question\":\"What experimental approaches were used to test causality in CKD models?\",\"answer\":\"The study used a 5/6 nephrectomy mouse model and locally delivered AAV-MIF to suppress MIF in renal tissue. In vitro work with CKD-derived MIF/proteins tested effects on Th17/Treg cells, and ISO-1 partially reversed those changes.\"}]","MIF Regulates the Th17/Treg Ratio to Exacerbate Kidney Injury in Chronic Kidney Disease - Research | PDF",1790694998,38]