Abstract: Certain aspects of the present disclosure provides systems, compositions, and methods for regulating expression or activity of an endogenous cytokine of a cell. In some cases, the present disclosure provides a system comprising an actuator moiety capable of complexing with a target gene encoding the endogenous cytokine to regulate expression or activity of the endogenous cytokine. The actuator moiety can be heterologous to the cell. The actuator moiety can be activatable upon exposing the cell to an external stimulus. Upon the exposure of the cell to the external stimulus, the actuator moiety can be activated to regulate expression or activity of the endogenous cytokine.