Zfp335 regulates the proportion of effector Treg and tumor immunity.
- Author:
Xiaonan SHEN
1
;
Wenhua LI
2
;
Xiaoxuan JIA
2
;
Biao YANG
2
;
Xin WANG
3
;
Haiyan LIU
2
;
Anjun JIAO
2
;
Lei LEI
2
;
Xiaofeng YANG
4
;
Baojun ZHANG
5
Author Information
1. Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061; Genertec Universal Xi'an Aero-Engine Hospital, Xi'an 710021, China.
2. Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
3. Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
4. Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. *Corresponding authors, E-mail: yangxiaofeng@xjtu.edu.cn.
5. Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061; Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. *Corresponding authors, E-mail: bj.zhang@mail.xjtu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
T-Lymphocytes, Regulatory/metabolism*;
Mice;
CD8-Positive T-Lymphocytes/immunology*;
Neoplasms/genetics*;
Cell Line, Tumor;
Mice, Inbred C57BL;
Mice, Knockout;
DNA-Binding Proteins/genetics*;
Female
- From:
Chinese Journal of Cellular and Molecular Immunology
2025;41(5):385-390
- CountryChina
- Language:Chinese
-
Abstract:
Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335fl/fl FOXP3creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4+ T cells, CD8+ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4+ and CD8+ T cells, along with their respective effector cells, was significantly higher in the Zfp335CKO group than in the WT group. The proportions of CD4+ and CD8+ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335CKO group compared to that of the WT group. In addition, the percentage of CD8+ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)+ Treg in the Zfp335CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
