There now exists strong genetic and functional evidence that RNA/DNA immune-complexes found in lupus patients can drive IFN-α production through the activation of TLR7 or TLR9 [85], respectively, indicating that TLR7/9 activation may be an important primary trigger for the generation of autoimmune disease (reviewed in [5, 86]). The gene discussed is TLR9; the disease is systemic lupus erythematosus.