As we hypothesized, ablation of miR-146a, which resulted in significantly increased Smad2, Smad3 and Smad4 levels, led to significantly increased recruitment of Smad2, Smad3 and Smad4 transcription factors to the Iα promoter in B cells activated by LPS or CD154 plus IL-4, IL-5, TGF-β, anti-δ mAb and RA, and as analyzed by specific ChIP (Figure 8B). Here, SMAD4 is linked to rheumatoid arthritis.