IL-4/IL-13 Responsive STAT6 Luciferase Reporter THP-1 Cell Line

IL-4/IL-13 Responsive STAT6 Luciferase Reporter THP-1 Cell Line is a THP-1 cell line with stably integrated Firefly luciferase reporter under the control of STAT6 (signal transduced and activator of transcription factor 6) response element, resulting in a fully functional IL-4 (interleukin-4)/IL-13 mediated signaling pathway through STAT6. This cell line has been validated in activation assays with human IL-4 and IL-13, and tested with an anti-IL-4R antibody (e.g. Dupilumab), an anti-IL-13 Ab (e.g. Lebrikizumab), a STAT6 inhibitor, and a STAT6-directed PROTAC (proteolysis targeting chimera). The transcription factor STAT6 (signal transduced and activator of transcription factor 6) plays a vitally important role in immune cells. IL-4-activated STAT6 signaling is required for Th2 differentiation and immunoglobulin class switching and also mediates direct repression of inflammatory enhancers in macrophages. STAT6 is involved in several aspects of allergic inflammatory disease, like airway hyperresponsiveness, eosinophilic infiltration, and mast cells responses. STAT6 is activated primarily by IL-4 and the related IL-13, with have overlapping biologic profiles. Upon IL-4 and IL-13 binding, the receptor complex composed of IL-4Ralpha and IL-13Ralpha1 activates the receptor-associated Janus kinases (JAK1 and Tyk2), leading to the activation of STAT6. Activated STAT6 forms homodimers that translocate to the nucleus where they bind the promoter of responsive genes, inducing gene transcription. While both cytokines activate STAT6 signaling, IL-4 is more potent than IL-13. Dysfunction of the STAT6 pathway leads to allergic reactions (asthma, atopic dermatitis, food allergies) and cancer (Hodgkin, central nervous system, and follicular lymphoma). Inhibitors have been shown to reduce acute inflammation in animal models, and future developments may lead to new therapeutical tools for STAT6 related pathologies.