The IL13 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population from the 786-O renal cell adenocarcinoma line, with targeted disruption of the IL13 gene. This model eliminates endogenous IL13 expression, enabling dissection of IL13-mediated signaling in a clear cell renal cell carcinoma (ccRCC) background. The polyclonal format avoids clonal artifacts while ensuring consistent gene-level knockout.
The 786-O line, derived from a primary clear cell adenocarcinoma, carries a VHL tumor suppressor mutation, a hallmark of ccRCC. These epithelial cancer cells exhibit dysregulated HIF pathways and constitutive angiogenic and invasive programs. Widely used to study ccRCC, this background provides a clinically relevant context for exploring how IL13 loss impacts renal oncogenesis and immune modulation.
IL13 is an immunoregulatory cytokine signaling through IL13RA1/IL4RA receptor complexes, with IL13RA2 acting as a decoy. Upon binding, it activates JAK1 and JAK3, leading to STAT6 phosphorylation and nuclear translocation, which drives transcription of targets like SOCS1 and CCL11. IL13 also recruits IRS1 to stimulate PI3K-AKT and MAPK/ERK via MAPK1/3. Upstream, IL13 expression is regulated by T cell activation, GATA3, NFAT, and a STAT6 autoregulatory loop, with IL4 as a key inducer.
In 786-O cells, IL13 knockout abrogates IL13-induced JAK-STAT6 and PI3K/AKT signaling, impairing anti-inflammatory and pro-tumorigenic responses. ccRCC tumors often exploit IL13-mediated immune evasion and aberrant STAT6 activation. Eliminating IL13 in this VHL-mutant background allows investigation of Th2-driven effects on proliferation, apoptosis resistance, and immune crosstalk, particularly regarding therapeutic resistance involving JAK/STAT and PI3K/AKT pathways.
Applications include western blotting for STAT6 phosphorylation, RT-qPCR for IL13 targets (SOCS1, CCL11), and RNA-seq to profile transcriptomic changes. The cells support JAK inhibitor screening via proliferation, apoptosis, and drug sensitivity assays, as well as migration/invasion studies and flow cytometry for cytokine receptors. Co-culture with immune cells models IL13-dependent immune evasion. For custom inquiries, contact Ascent Research.
