As an unconventional transcription factor in TIR signaling, C/EBPβ and its target genes (TNF, Csf3, S100a8) were intimately linked to innate immune cell expansion, and host factor-derived inflammation in RA may account for, at least in part, the proinflammatory cytokine networks and tissue-damaging cellular activities in synovitis observed in SIGIRR-deficient mice. Here, TNF is linked to rheumatoid arthritis.