The IL4R Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 786-O cell line, with targeted disruption of the IL4R gene encoding the interleukin-4 receptor alpha chain. This product provides a heterogeneous pool of cells bearing IL4R gene disruptions for consistent loss-of-function analyses across cell batches, avoiding the selection bottlenecks and clonal artifacts often observed in single-cell-derived clones.
The parental 786-O cell line is a well-characterized human renal proximal tubule epithelial adenocarcinoma line, originally established from a primary clear cell renal cell carcinoma (ccRCC). It serves as a widely used in vitro model for renal cancer biology, exhibiting key genetic and phenotypic features of ccRCC, including dysregulation of hypoxia and metabolic pathways. Its epithelial origin and tumorigenic properties make it suitable for studying tumor?Cmicroenvironment crosstalk and cancer cell signaling.
IL4R is a critical receptor subunit that binds interleukin-4 and interleukin-13, forming signaling complexes with the common gamma chain or IL-13R??1, respectively. Ligand engagement triggers activation of the associated tyrosine kinases JAK1 and JAK3, which phosphorylate STAT6. Phosphorylated STAT6 dimerizes and translocates to the nucleus, where it promotes the expression of target genes such as CCL17, CCL22, and SOCS1. This signaling axis is central to type 2 helper T cell (Th2) differentiation, B cell activation, and allergic inflammation, and is subject to regulation by upstream factors including the transcription factor GATA3.
In the context of 786-O cells, IL4R signaling is implicated in the response to Th2-polarized cytokine milieus that may be present in the renal tumor microenvironment. Disruption of IL4R in this cell line allows researchers to dissect how IL-4/IL-13 signaling influences ccRCC cell proliferation, survival, or immune modulatory functions. The knockout model can help elucidate the role of IL4R in shaping the tumor immune landscape, potentially revealing mechanisms of immune evasion and identifying actionable nodes for therapeutic intervention in renal cell carcinoma.
Key applications include screening of small-molecule inhibitors or biologics targeting the IL-4/IL-13?CJAK?CSTAT6 pathway, and evaluating cytokine response signatures by measuring STAT6 phosphorylation via western blotting or flow cytometry. The polyclonal knockout cells are well suited for co-culture experiments with immune cells to study paracrine loops and for RT-qPCR profiling of IL-4/IL-13-inducible genes like CCL17 or SOCS1. Their utility spans tumor immunology, drug discovery, and functional validation of signaling crosstalk. For further technical details or to discuss custom applications, please contact Ascent Research.
