The Effects of WW2/WW3 Domains of Smurf2 Molecule on CD4+CD25+/CD4+ Proportion in Spleen of 4T1 Tumor Bearing BALB/c Mice

Background: TGF-β has long been considered as the main inducer of Tregs in tumor microenvironment and is the reason for the aberrant number of Tregs in tumor-bearing individuals. Recently, it has been suggested that the enzyme arginase I is able to mediate the induction of Tregs in a TGF-β-independent fashion. The recombinant WW2/WW3 domains from smad ubiquitination regulatory factor 2 molecule was demonstrated to increase TGF-β signaling while reducing arginase I gene expression. In this study, we aimed to examine the effects of this recombinant protein on CD4+CD25+/CD4+ proportion in the spleen of 4T1 mammary carcinoma-bearing BALB/c mice. Methods: Flow cytometry was used to evaluate CD4+CD25+ spleen cell populations of the tumor-bearing mice that received WW2/WW3 protein treatment and those of the control group. Results: The results indicated a significant rise in CD4+CD25+/CD4+ ratio, along with an average increase in tumor mass of the subjects that underwent protein treatment. Conclusion: It can be inferred that the heightened CD4+CD25+/CD4+ proportion in the spleen of  protein-treated tumor-bearing mice can be the result of the increased TGF-β signaling despite the reduced arginase I expression.