In TREML4 -/- mice macrophages that are hyporesponsive to TLR7 agonists, macrophages fail to produce type I interferons due to impaired phosphorylation of the transcription factor STAT1 by the mitogen-activated protein kinase p38 and decreased recruitment of the adaptor MYD88 to TLR7. TREML4 deficiency reduced the production of inflammatory cytokines and autoantibodies in MRL/lpr mice, suggesting that TLR7 is a vital component of antiviral immunity and a predecessor factor in the pathogenesis of rheumatic diseases such as systemic lupus erythematosus (SLE).
In TREML4 -/- mice macrophages that are insensitive to TLR7 stimuli, macrophages do not produce type I interferons because of impaired activation of the transcription factor STAT1 by p38 MAPK and reduced recruitment of MYD88 to TLR7. The lack of TREML4 led to decreased production of inflammatory cytokines and autoantibodies in MRL/lpr mice, suggesting that TLR7 plays a vital role in antiviral immunity and is an early factor in the progression of rheumatic diseases like SLE.