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^fl/fl FOXP3^creERT2), 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 Zfp335^CKO 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 Zfp335^CKO 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 Zfp335^CKO 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 Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO 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^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
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

【Objective】 To evaluate the effect of Arntl on T cell development and T cell-mediated anti-viral immunity. 【Methods】 Arntl^F/FCD4cre⁺(KO) in mice was constructed to delete Arntl gene specifically in T cells. We examined the percentage and number of T cell subsets in the thymus and spleen by flow cytometry (FCM). At day 8 after lymphocytic choriomeningitis virus (LCMV) infection, the proportions of T cell subsets, virus-specific CD8⁺ T cells and IFN-γ secreting T cells were analyzed. The viral load in the spleen was measured using qPCR. Naive CD4⁺ T cells (CD4⁺CD25^-CD44^-CD62L⁺) were sorted by flow cytometry to perform T helper cell differentiation in vitro. 【Results】 The percentage and number of T cells in the thymus and spleen of KO mice showed no significant change compared with those in the control group (Arntl^F/FCD4cre^- mice, WT) (P>0.05). Acute LCMV infection did not cause observable changes in effector T cell proportion in the spleen of KO mice compared to that in WT mice (P>0.05), but KO mice showed a higher proportion of IFN-γ secreting T cells (P<0.05) and better virus clearance (P<0.05). In addition, naive CD4⁺ T cells from KO mice were more prone to differentiate into Th1 cells in vitro (P<0.05). 【Conclusion】 Arntl deletion in T cells does not affect T cell development, but enhances their ability to defend against viral infection by promoting Th1 cell differentiation and response.

Objective To evaluate the effects of nasolabial flap with facial artery and its branches perforator for reconstruction of nasal defect.Methods Between March 2013 and April 2017,21 patients underwent operations for the reconstruction of nasal defect,caused by trauma,surface tumors,moles and infection.The size of the defect was 1.5 cm × 2.0 cm to 3.0 cm × 3.0 cm.Designed various nasolabial perforator flap was pedicled with the facial artery.The pulsed blood flow detector determined the location of the facial artery and its perforation position,which was the rotation point,and the rotation of the nasolabial fold flap covered the nasal defect area to repair.Results 21 flaps survived.Surface artery perforation nasolabial fold flap was good blood supply,of which 1 case of flap was congested and recovered after treatment.After 1 month to 3 years follow-up on 21 cases,20 cases showed good results and 1 case had generally accepted.The color,shape and function of the flap were significant,similar to the normal skin.Conclusions A small area defect in the nose is preferred by using facial arterial perforation nasolabial fold flap repair,which does not need secondary repair,and is worthy of clinical application.