IL17RA Knockout HT29 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human colorectal adenocarcinoma cell line HT29, designed for functional disruption of the IL17RA gene. This product provides a heterogeneous pool of gene-edited cells, enabling the study of IL-17 receptor A loss-of-function in a well-characterized epithelial tumor model. The CRISPR/Cas9 system was used to introduce targeted genomic modifications, resulting in a polyclonal knockout model suitable for investigating downstream signaling and biological consequences without reliance on single-cell clones. Researchers can utilize this population to assess IL17RA-dependent mechanisms in colorectal cancer biology, inflammatory signaling, and therapeutic development.
The parental HT29 cell line originates from a primary human colorectal adenocarcinoma and exhibits epithelial morphology, making it a widely employed model for colon cancer research. These cells retain numerous features of intestinal epithelial cells and are commonly used to study tumor cell biology, drug responses, and host-pathogen interactions. HT29 cells endogenously express IL17RA, allowing physiologically relevant interrogation of IL-17 signaling in the context of transformed colonic epithelium. The knockout variant thus offers a clean genetic background to dissect receptor-specific contributions in this setting.
IL17RA encodes the receptor subunit for the pro-inflammatory cytokines IL-17A and IL-17F, acting as a critical mediator of immune signaling. Upon ligand binding, IL17RA forms a heterodimer with IL17RC and recruits the adaptor protein ACT1 (TRAF3IP2), which in turn engages TRAF6 to activate downstream cascades. This receptor complex promotes NF-??B and MAPK (ERK, JNK, p38) pathways, leading to transcriptional induction of inflammatory mediators such as IL6, CXCL8, and CCL20. Additionally, expression of IL17RA can be upregulated by TNF-??, linking it to broader inflammatory networks. Key pathway components include the IKK complex, NF-??B p65, and AP-1 transcription factors, collectively driving pro-inflammatory gene expression. Disruption of IL17RA therefore abolishes the primary receptor for IL-17, severing these signaling connections and impairing downstream transcriptional responses.
In HT29 colorectal cancer cells, IL17RA knockout directly blocks IL-17-mediated activation of NF-??B and MAPK pathways, as IL-17 signaling is known to promote inflammatory gene expression and tumor-supportive functions in the colonic epithelium. By preventing the induction of cytokines and chemokines such as IL-6 and CXCL8, this knockout model reduces the protumorigenic and inflammatory responses typical of colorectal adenocarcinoma cells. This disruption is particularly relevant for studying the interplay between chronic inflammation and cancer progression, as IL-17 signaling has been implicated in tumor growth, angiogenesis, and immune cell recruitment within the colorectal tumor microenvironment. The model allows dissection of IL-17-dependent versus independent contributions to malignant phenotypes.
This knockout product is ideally suited for a range of investigative applications, including exploration of IL-17 signaling in colorectal cancer biology, inflammation-driven carcinogenesis, and high-throughput drug screening for anti-inflammatory or anticancer compounds. Researchers can employ techniques such as western blotting for phosphorylated NF-??B and MAPKs, RT-qPCR analysis of downstream targets like IL6 and CXCL8, ELISA-based cytokine secretion profiling, NF-??B luciferase reporter assays, and cell migration experiments to characterize functional outcomes. The polyclonal nature of the cells may also be leveraged to study population-level heterogeneity in signaling responses. For more information or to request this product, please contact Ascent Research.
