Gene expression profiles of LPS-stimulated RAW264.7 macrophages overexpressing Tbc1d23 novel innate immune gene

We previously identified Tbc1d23 as a candidate novel regulator of innate immunity using comparative genomics RNAi screens in C. elegans and mouse macrophages. Using mice with an engineered knockout mutation in Tbc1d23 and macrophages engineered to overexpress Tbc1d23, we now show that Tbc1d23 is a general but not universal inhibitor of the innate immune response, inhibiting multiple Toll-like receptor (TLR) and Dectin signaling pathways but not NOD signaling pathways. Tbc1d23 likely acts downstream of the TLR signaling adaptors MyD88 and Trif and upstream of the transcription factor XBP1. Importantly, like XBP1, Tbc1d23 affects the maintenance but not initiation of inflammatory cytokine production induced by lipopolysaccharide (LPS). The identification of a novel temporal regulator of innate immunity signaling validates the comparative genomics approach for innate immunity gene discovery. Total of 24 samples; Tbc1d23-overexpressing line and control line; 0, 1, 3, and 5 hour LPS treatment; 3 biological replicates per group