The y-linked autoimmune accelerating (yaa) locus is a potent autoimmune disease 
allele. Transcription profiling of yaa-bearing B cells revealed the 
overexpression of a cluster of X-linked genes that included Tlr7. FISH analysis 
demonstrated the translocation of this segment onto the yaa chromosome. The 
resulting overexpression of Tlr7 increased in vitro responses to Toll-like 
receptor (TLR) 7 signaling in all yaa-bearing males. B6.yaa mice are not overtly 
autoimmune, but the addition of Sle1, which contains the autoimmune-predisposing 
Slam/Cd2 haplotype, causes the development of fatal lupus with numerous 
immunological aberrations. B6.Sle1yaa CD4 T cells develop the molecular 
signature for T(FH) cells and also show expression changes in numerous cytokines 
and chemokines. Disease development and all component autoimmune phenotypes were 
inhibited by Sles1, a potent suppressor locus. Sles1 had no effect on 
yaa-enhanced TLR7 signaling in vitro, and these data place Sles1 downstream from 
the lesion in innate immune responses mediated by TLR7, suggesting that Sles1 
modulates the activation of adaptive immunity in response to innate immune 
signaling.