{"title":"[Zfp335调节效应Treg和肿瘤免疫的比例]。","authors":"Xiaonan Shen, Wenhua Li, Xiaoxuan Jia, Biao Yang, Xin Wang, Haiyan Liu, Anjun Jiao, Lei Lei, Xiaofeng Yang, Baojun Zhang","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>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 (Zfp335<sup>fl/fl</sup> FOXP3<sup>creERT2</sup>), 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<sup>+</sup> T cells, CD8<sup>+</sup> 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 Zfp335<sup>CKO</sup> group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, along with their respective effector cells, was significantly higher in the Zfp335<sup>CKO</sup> group than in the WT group. The proportions of CD4<sup>+</sup> and CD8<sup>+</sup> T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335<sup>CKO</sup> group compared to that of the WT group. In addition, the percentage of CD8<sup>+</sup> T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335<sup>CKO</sup> group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)<sup>+</sup> Treg in the Zfp335<sup>CKO</sup> group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335<sup>CKO</sup> 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 Zfp335<sup>CKO</sup> mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.</p>","PeriodicalId":61378,"journal":{"name":"细胞与分子免疫学杂志","volume":"41 5","pages":"385-390"},"PeriodicalIF":0.0000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Zfp335 regulates the proportion of effector Treg and tumor immunity].\",\"authors\":\"Xiaonan Shen, Wenhua Li, Xiaoxuan Jia, Biao Yang, Xin Wang, Haiyan Liu, Anjun Jiao, Lei Lei, Xiaofeng Yang, Baojun Zhang\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 (Zfp335<sup>fl/fl</sup> FOXP3<sup>creERT2</sup>), 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<sup>+</sup> T cells, CD8<sup>+</sup> 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 Zfp335<sup>CKO</sup> group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, along with their respective effector cells, was significantly higher in the Zfp335<sup>CKO</sup> group than in the WT group. The proportions of CD4<sup>+</sup> and CD8<sup>+</sup> T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335<sup>CKO</sup> group compared to that of the WT group. In addition, the percentage of CD8<sup>+</sup> T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335<sup>CKO</sup> group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)<sup>+</sup> Treg in the Zfp335<sup>CKO</sup> group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335<sup>CKO</sup> 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 Zfp335<sup>CKO</sup> mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.</p>\",\"PeriodicalId\":61378,\"journal\":{\"name\":\"细胞与分子免疫学杂志\",\"volume\":\"41 5\",\"pages\":\"385-390\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"细胞与分子免疫学杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"细胞与分子免疫学杂志","FirstCategoryId":"3","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
[Zfp335 regulates the proportion of effector Treg and tumor immunity].
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.