In addition, acidic pH in endosomes caused by defective localization of NCF1 activates TLR signaling in plasmacytoid dendritic cells (pDCs), the principal producer of type I IFNs, leading to increased IFN secretion and thereafter more severe disease in the imiquimod-induced lupus model (12, 15–17). Here, IFNA1 is linked to systemic lupus erythematosus.