These observations suggest that pDCs not only function as upstream initiators of IFN-I-associated inflammation by activating Ly6Chigh monocytes, but also trigger autoimmunity through unabated activation of cDCs depending on the IFNAR1- and CD40-mediated signaling, which stimulate autoreactive T cells and the differentiation of autoreactive B cells into Ab-secreting plasma cells for development of the pathogenesis of lupus-like disease. The gene discussed is IFNAR1; the disease is Autoimmunity.