In findings posted online ahead of publication in Proceedings of the National Academy of Sciences (PNAS), scientists at Cincinnati Children’s Hospital Medical Center report a novel process of coordinated cellular communications vital to the maintenance of T cells. If the process breaks down, T cells proliferate rapidly and die off. This could disrupt the immune system’s normal defensive functions.
“This study involves an important mechanistic finding affecting the molecular regulation of T cell biology that will have implications in our future understanding of immunodeficiency and autoimmunity,” said Yi Zheng, Ph.D., co-investigator on the study and director of Experimental Hematology/Cancer Biology at Cincinnati Children’s.
T cells – named such because they originate in the thymus – are a type of white blood cell vital to the body’s immune system and its defense against pathogens and disease.
Scientists entered the current study knowing from earlier research that normal T cell biology involves carefully coordinated signaling between what are known as T cell receptors and a gene/protein called interluken-7 receptor (IL-7Ra). IL-7Ra is vital to the formation of white blood cells called lymphocytes, which include T cells. Unknown before this study, however, were the detailed mechanisms that regulate this coordination.
In a variety of test tube experiments and experiments involving mice, researchers determined the cell division control protein Cdc42 is essential to coordinating a signaling network of genes/proteins and enzymes that control normal T cell biology.
The disruption caused by loss of Cdc42 included restricted signaling by IL-7Ra, an initial hyper-proliferation of T cells and their rapid loss through programmed cell death. When the researchers were able to reconstitute Cdc42 in their experiments, T cell biology became more normalized, they report.
The study was led by Fukun Guo, Ph.D., in the division of Experimental Hematology/Cancer Biology at Cincinnati Children’s. The scientists plan to follow up their study by looking for additional details about the molecular pathways affected through Cdc42’s central regulatory role in T cell biology. They also want to look for Cdc42’s potential application to new diagnostic or therapeutic approaches for diseases affecting the immune system.
Source: Nick Miller
Cincinnati Children’s Hospital Medical Center