IL1RL1 Knockout Cell Line (HCT116)

The choice depends on whether you are studying IL1RL1 (ST2)'s role as the IL-33 receptor or modeling its functions in Th2 immunity and asthma. The Knockout line is the standard tool for asking whether ST2 is required for IL-33 signaling — IL1RL1 partners with IL1RAP to form the IL-33 receptor complex; upon IL-33 binding, the complex assembles and activates MyD88-IRAK-NF-κB signaling, driving Th2 cytokine production and ILC2 activation. Overexpression is useful for studying ST2 in heterologous expression contexts. Important consideration: IL1RL1 is principally expressed in mast cells, Th2 cells, ILC2s, basophils, and eosinophils — HCT 116 is not the canonical physiological context, but HCT 116 has been characterized for IL-33-ST2 signaling in colorectal cancer biology. The EDITGENE IL1RL1 Knockout in HCT 116 enables study of IL-33-ST2 signaling in colorectal cancer context. Rescue with wild-type or IL1RAP-binding-deficient ST2 is the standard specificity control. The knockout is a critical specificity tool for tezepelumab (anti-TSLP, indirect effect on ST2 pathway, FDA-approved for severe asthma) and astegolimab/itepekimab/etokimab (anti-ST2/IL-33 antibodies in clinical development for asthma and atopic dermatitis).

Primary applications: • IL-33-ST2 signaling: phospho-IκBα, NF-κB activation, and Th2 cytokine target gene (IL5, IL13) expression following IL-33 stimulation in ST2-null cells. • Asthma drug specificity: critical genetic control for astegolimab (anti-ST2), itepekimab and etokimab (anti-IL-33) in clinical development for severe asthma and atopic dermatitis. • Colorectal cancer biology: in CRC-relevant studies, IL-33-ST2 signaling effects on tumor proliferation and immune microenvironment. • ST2 soluble vs membrane forms: sST2 (soluble decoy) versus full-length ST2 functional dissection through differential rescue. EDITGENE recommends this model for researchers investigating IL-33-ST2 signaling, Th2-driven inflammatory disease, and ST2-targeted asthma/AD drug development.

Yes. ST2 rescue experiments require attention to receptor architecture and isoforms: • Construct design: use a codon-modified IL1RL1 sequence with a small intracellular C-terminal tag (FLAG, HA). IL1RL1 has long (ST2L, full-length membrane-bound) and short (sST2, soluble) isoforms with different functions — choose the isoform appropriate to the experimental question. • Surface localization validation: confirm plasma membrane localization for ST2L isoform; confirm secretion for sST2. • IL1RAP-binding-deficient rescue: extracellular domain mutations disrupt IL1RAP co-receptor partnership. • Functional readout: rescue should restore IL-33-induced phospho-IκBα and Th2 cytokine target gene expression (for ST2L) or IL-33 sequestration (for sST2). HCT 116 transduces efficiently with lentivirus and supports stable rescue line generation.