Cutaneous lupus erythematosus: The impact of self‐amplifying innate and adaptive immune responses and future prospects of targeted therapies

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease encompassing a broad spectrum of skin conditions including localized plaques or widespread lesions, which may be accompanied by systemic involvement (systemic lupus erythematosus (SLE)). The disease is characterized by necroptotic keratinocytes and a cytotoxic immune cell infiltrate at the dermo-epidermal junction (DEJ), orchestrated by interferon (IFN)-regulated proinflammatory cytokines. Molecular analyses revealed a strong upregulation of innate and adaptive immune pathways in lesional skin including DNA-recognition pathways, chemokine signalling, antigen presentation and B- and T-cell activation, which are believed to interact in a complex self-amplifying network. Concerning adaptive immune signalling, particularly B cells are currently being studied as there is growing evidence for additional abilities besides autoantibody expression in skin autoimmunity. These detailed insights have paved the way for the development of drugs targeting crucial molecules of pathogenic immune cells and pathways. Moreover, they forwarded the understanding of distinct molecular mechanisms within CLE subtypes, which might enable a more mechanism-directed, stratified pharmacotherapy of LE skin lesions in the future.