Transcriptomic profiles of ligand-stimulated IRF-knockout THP1 cells

Interferon regulatory factors (IRFs) are essential for transcription of
interferons (IFNs), interferon-stimulated genes (ISGs), and
pro-inflammatory cytokines. We profile the transcriptome of human monocyte
THP1 cells challenged with cGAMP, LPS, or IFNB1 protein as a function of
knockout (KO) or overexpression (OE) of IRFs or KO of IFNAR2. We define
distinct gene expression groups, reflecting the transcription factors
responsible for their induction, including subgroups activated by more
than one pathway or feed-forward regulation. We compare IRF3- and
IRF7-induced gene signatures and note the strong direct induction of a
subset of antiviral-acting ISGs by IRF3 or IRF7. LPS treatment induces
NF-kB responses in monocyte and macrophage state cells; however, IFNs and
ISGs are only co-induced in the macrophage state, requiring IRF3. IRF1,
IRF2, IRF5, and IRF8 are largely dispensable for IFN-stimulated or
innate-immune-mediated gene induction. This study provides a valuable
resource for dissecting complex inflammatory gene signatures and their
underlying transcription factors, thereby anticipating the effects of
selectively drugging the underlying pathways.