UCP2 Deficiency Renders Th1/2 Pathogenic Phenotype to CD4+ T cells

Abstract

Abstract Uncoupling protein 2 (UCP2) is an anion transporter in the mitochondrial matrix that controls ROS production, calcium influx, and C4 metabolites. It is regarded as a metabolic regulator. A lack of UCP2 has led to an extreme clinical score with higher oxidative stress and inflammation in autoimmune illness, even though elevated UCP2 has been found in many tumors and is known to be a potential target for tumor therapy. Uncertainty still exists regarding UCP2’s function in T cells. A significant rise in the Th2/Th1 ratio was seen in this work using CD4 cells from UCP2−/− mice. These cells exhibited an improved Th2 phenotype with decreased calcium influx, elevated iNOS expression, and elevated urea metabolism. CD4 cells were treated with NOC-18, a source of nitric oxide, or Genipin to demonstrate nitric oxide-mediated Th2 polarization (inhibitor for UCP2). There were more cytotoxic markers and Th2/Th1 double positive cells. The B16/F10 tumor cells were controlled in vitro in a tumor killing assay utilizing genipin-treated CD4 cells, according to the findings. However, in UCP2−/− mice, the severity of EAE worsened, and heterogenic Th2 cells were infiltrated into central nerves system. Our findings imply that the loss of UCP2 in CD4 increases Th2 polarization with a cytotoxic phenotype and may be relevant to various illnesses. R01 CA250458, R01 CA236379