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  3. MIF Regulates the Th17/Treg Ratio to Exacerbate Kidney Injury in Chronic Kidney Disease

MIF Regulates the Th17/Treg Ratio to Exacerbate Kidney Injury in Chronic Kidney Disease

  • Inflammation. 2025 Dec 23;49(1):15. doi: 10.1007/s10753-025-02418-x.
Ruijing Zhang # 1 2,  Keyi Fan # 2 3,  Heng Wang 2 3,  Jinshan Chen 2 3,  Chuanlong Lu 2 3,  Lizheng Li 2 3,  Runze Chang 2 3,  Maolin Qiao 2 3,  Yuhang Zhang 2 3,  Hongjiu Zhang 2 3,  Yaling Li 2 3,  Jie Zhang 2 3,  Yijie Ning 2 3,  Honglin Dong 4 5
Affiliations

Affiliations

  • 1 Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
  • 2 Vascular Institute of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi, China.
  • 3 Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
  • 4 Vascular Institute of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi, China. [email protected].
  • 5 Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China. [email protected].
  • # Contributed equally.
PMID: 41436686 DOI: 10.1007/s10753-025-02418-x
Abstract

Chronic kidney disease (CKD) is characterized by gradual and progressive deterioration of renal function over time, and its pathogenesis is strongly associated with immune cell imbalance, Th cell diversification, and oxidative stress. 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 < 0.01) in CKD patients compared to normal controls. MIF levels also correlated with renal parameters (Crea, p < 0.001; BUN, p < 0.0001; EGFR, p < 0.0001). In vitro experiments confirmed a significant increase (p < 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 < 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.

Keywords

Chronic kidney disease (CKD); Helper t cells (Th17); Macrophage migration inhibitory factor (MIF); Regulatory t cells (Tregs).

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