A Phenotypic Screening Approach Using Human Treg Cells Identified Regulators of Forkhead Box p3 Expression
Abstract
Regulatory T (Treg) cells, expressing the transcription factor forkhead box p3 (FOXP3), are the key cells regulating peripheral autoreactive T lymphocytes by suppressing effector T cells. FOXP3+ Treg cells play essential roles controlling immune responses in autoimmune diseases and cancer. Several clinical approaches (e.g., polyclonal expansion of Treg cells with anti-CD3 and anti-CD28 coated beads in the presence of drugs) are under evaluation. However, expression of FOXP3, recognized as the master regulator of Treg cells, in induced Treg cells have been shown to be instable, and molecular targets involved in regulating FOXP3 expression and Treg cell function have not been well-defined. Thus, new targets directly regulating FOXP3 expression and the expression of its downstream genes (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA4)) have the potential to stabilize the Treg cell phenotype and function. This report describes the development of an automated medium-throughput 384-well plate flow cytometry phenotypic assay meauring the protein expression of FOXP3 and CTLA4 in human Treg cells. Screening a library of 4213 structurally diverse compounds allowed us to identify a variety of compounds regulating FOXP3 and CTLA4...Continue Reading
References
Glycogen synthase kinase 3β inhibition promotes human iTreg differentiation and suppressive function
Citations
Related Concepts
Related Feeds
Autoimmune Diseases
Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.