Systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) of the skin are autoimmune diseases characterized by inappropriate immune responses against self-proteins whereas the key elements that determine disease pathogenesis and progression are largely unknown. Recently, we and others described a novel immune checkpoint molecule belonging to the B7/CD28 gene family – named programmed death-1 homolog (PD-1H) or V-domain Ig-containing Suppressor of T cell activation (VISTA) – that functions to control T cell activation. Here we show that mice lacking immune inhibitory receptor PD-1H on spontaneously develop cutaneous and systemic autoimmune diseases resembling lupus. Furthermore, cutaneous lupus lesions of PD-1H KO mice share a similar skin-infiltrate to both the canonical murine model of lupus, MRL/lpr mice, as well as human DLE. Using mass cytometry, we identified neutrophils as critical early immune infiltrating cells within cutaneous lupus lesions of PD-1H KO mice that exhibit proinflammatory phenotypes. We also found that PD-1H is highly expressed on immune cells in human SLE, DLE lesions and cutaneous lesions of MRL/lpr mice. PD-1H agonistic monoclonal antibody in MRL/lpr mice reduces cutaneous disease, autoantibodies, inflammatory cytokines, chemokines and pathogenic T cells. Furthermore, PD-1H on both T cells and myeloid cells could transmit inhibitory signals resulting in reduced activation and function, establishing PD-1H as an inhibitory receptor on T cells and myeloid cells. On the basis of these findings, we propose that PD-1H is a critical element in the pathogenesis and progression of lupus and PD-1H agonist could be effective for treatment of systemic and cutaneous lupus.