Keratinocytes - Amplifiers of Immune Responses in Systemic Lupus Erythematosus

Epithelial cells have been acknowledged as important players in autoimmune diseases by directing and enhancing inflammatory responses. Here, we summarize recent publications that examine keratinocyte (KC) dysfunction and its contribution to cutaneous and systemic disease in systemic lupus erythematosus patients.

Chronic upregulation of type I interferon (IFN) in KCs is a feature of both lesional and nonlesional lupus skin. This IFN rich environment modulates epidermal cell death responses and promotes inflammatory responses to UV light exposure. In addition, newer technologies such as single cell RNA-seq are informing our understanding of lupus-specific intercellular crosstalk and how this contributes to disease. Recent discoveries in KC dysfunction in lupus skin include aberrant IFN responses to environmental stress, enhanced cytokine and chemokine secretion and epigenetic changes leading to increased cell death. Further research will enable precision therapies for lupus treatment.