Epithelial human NLRC4 promotes cancer survival by mediating Type-I Interferon signaling and immune infiltration
The induction of a broad Type-I IFN gene signature by NLRC4 is confirmed with a NLRC4 GOF mutation (T337S), using a THP1-NLRC4 (T337)-expressing stable cell line versus WT NLRC4.These Type-I IFN stimulated genes were confirmed to be also upregulated in NLRC4 (T337S) patient monocytes versus healthy controls, but not in NLRP3 (G569R) patient monocytes. Unbiased gene set enrichment analysis of RNAseq revealed a top enrichment of the “interferon alpha response” pathway in THP1-NLRC4 (T337S) cells versus WT NLRC4 Overall design: Primary human monocyte-derived macrophages and NLRC4-transduced THP1 cells were generated, then stimulated with PMA for up to 72hrs. Control (2), CEG, and NOMID patient PBMC-derived monocytes were stimulated with LPS and DOTAP/flagellin.