NF Erythroid 2-Related Factor 2 Deficiency Enhances the Immunosuppressive Function of Monocytic Myeloid-Derived Suppressor Cells in a Peroxisome Proliferator-Activated Receptor-γ-Dependent Manner

作者：Yichen Jia, Jiawei Li, Tianying Yang, Ruimin Li, Guo-Wei Tu, Yue Qiu, Xuepeng Zhang, Ruirui Sang, Yi Shi, Shihao Xu, Yin Celeste Cheuk, Jingjing Liu, Ruiming Rong, Yi Zhang · 发表于：Kidney360 · 年份：2025 · DOI：10.34067/kid.0000000947 · 被引用次数：2 · 研究领域：Immune cells in cancer、Immune Cell Function and Interaction、Immune Response and Inflammation

Key Points NF erythroid 2–related factor 2 (Nrf2) deficiency enhances the immunosuppressive function of monocytic myeloid-derived suppressor cells and ultimately ameliorates acute and chronic inflammatory disease in mice. The suppressive role of Nrf2−/− monocytic myeloid-derived suppressor cells could be attributed to increased levels of inducible nitric oxide synthase but decreased Arg1, the peroxisome proliferator-activated receptor- γ -dependent activation mechanism. Background Myeloid-derived suppressor cells (MDSCs) comprise monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (G-MDSCs), both of which are effective for controlling T-cell responses. Although NF erythroid 2–related factor 2 (Nrf2) participates in the expansion of MDSCs and MDSC-mediated immunosuppression, the underlying mechanisms of Nrf2 in MDSC differentiation remain poorly understood. Methods In this study, G-MDSCs or M-MDSCs were induced and sorted from the bone marrow of wild-type (WT) or Nrf2 −/− mice using flow cytometry in vitro , with or without GW9662 treatment. Mouse models of tumorigenesis, AKI, and CKD were used to evaluate the immunosuppressive function of WT or Nrf2 −/− M-MDSCs treated with or without GW9662. Histologic analysis was performed to evaluate tumor angiogenesis or kidney injury. Immunohistochemical staining was used to evaluate lymphocyte infiltration in kidney. Masson trichrome and Sirius red staining were performed to evaluate kidney fibrosis. In addition, RNA sequencing was conduc...