In systemic lupus erythematosus and cutaneous lupus, pDC-driven type I IFN and keratinocyte-derived IFN-κ form a feed-forward loop that elevates ISG signatures in blood and skin; this axis is therapeutically tractable, as evidenced by clinical benefit with IFNAR blockade and by pharmacodynamic suppression of ISGs [85]. Here, IFNAR1 is linked to systemic lupus erythematosus.