The IRF5 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population with targeted disruption of the IRF5 gene in the NCI-H1975 human lung adenocarcinoma cell line. This ready-to-use knockout pool is generated by transient Cas9/guide RNA expression, resulting in a heterogeneous cell population with IRF5 loss-of-function, avoiding single-cell cloning artifacts and preserving population diversity. The polyclonal format provides a robust model for studying IRF5-dependent pathways without the use of selective markers.
NCI-H1975 is an epithelial cell line derived from the pleural effusion of a non-smoking female patient with lung adenocarcinoma. It harbors EGFR L858R and T790M mutations, making it a key model for EGFR-mutant non-small cell lung cancer (NSCLC) and for studying tyrosine kinase inhibitor sensitivity and resistance. The cells maintain adenocarcinoma characteristics and are widely used in oncology research.
IRF5 is a transcription factor that orchestrates innate immune responses by inducing type I interferons (IFNA, IFNB) and proinflammatory cytokines (IL6, TNFA, CXCL10) downstream of TLR7 and TLR9. Signaling proceeds through MyD88, TRAF6, and the kinases IKK?? and TBK1, which phosphorylate IRF5. Dimerized IRF5 translocates to the nucleus and, in collaboration with NF-??B and IRF3, activates transcription of immune genes, forming the TLR?CMyD88?CTRAF6?CIKK?¨CIRF5 axis.
Disruption of IRF5 in the EGFR-mutant NCI-H1975 background enables investigation of cross-talk between oncogenic signaling and innate immune pathways. EGFR-driven signals may influence IRF5-mediated cytokine production, and loss of IRF5 can reveal its role in shaping the tumor microenvironment, immune cell recruitment, and response to therapy. This model is valuable for dissecting how inflammatory transcription factors contribute to EGFR-mutant NSCLC progression.
Applications include Western blotting and phospho-analysis for IRF5 and downstream effectors, RT-qPCR and ELISA for cytokine quantification (e.g., IFNA, IL6), RNA-seq for transcriptomic profiling, flow cytometry for immune checkpoint detection, and reporter assays for IRF5 activity. The cells are suited for drug sensitivity testing with EGFR inhibitors or immunomodulators, and for co-immunoprecipitation to study IRF5 interactions. For further technical information, please contact Ascent Research.
