The role of inflammatory cell death in type 1 dominant inflammatory skin diseases

While there has been significant progress in the development of new therapies for psoriasis and atopic dermatitis in recent years, innovation in the field of type 1 dominant skin diseases is still limited. This category comprises diseases characterized by a cytotoxic immune reaction directed against resident skin cells. The histological correlate is interface dermatitis, defined by a subepidermal inflammatory infiltrate associated with epidermal keratinocyte apoptosis. Representative conditions include lichen planus, cutaneous lupus erythematosus, erythema multiforme, alopecia areata, and vitiligo. Immunologically, there is a dominance of Th1 cells, which mediate their effects through interferon-γ and tumor necrosis factor-α. Recent findings have shown that, in addition to apoptosis, other forms of cell death are also activated by this immune response, such as necroptosis. In contrast to apoptosis, necroptosis represents a strong immunological stimulus and thus further intensifies the local inflammatory response. These findings open new therapeutic perspectives, as numerous necroptosis inhibitors are currently under investigation for various inflammatory diseases. The present review summarizes the immunopathogenesis of type 1-dominant skin diseases and highlights emerging therapeutic strategies, including the inhibition of inflammatory cell death.