Phenotypic Chemical Screening in CD4⁺ T Cells to Identify Epigenetic Inhibitors

Chemical biology provides an attractive approach to identify genes involved in a particular biological process. This screening approach has its advantages because the assays are usually non-destructive, and analysis can be performed even if the mechanism of action is unknown. During an immune reaction, cells upregulate the expression and secretion of small proteins called cytokines that have specific effects on the interactions and communication between cells. Here, we describe the principles and steps involved in the execution of chemical screening for identifying epigenetic inhibitors that affect cytokine production in differentiated Th1, Th2, and Th17 cells. Our approach provides a rationale for identifying epigenetic chemical compounds that are capable of controlling CD4⁺ T-cell cytokine function that may be beneficial for treating inflammatory diseases.