Fig. 1

Keratinocytes (KCs) produce cytokines and pro-inflammatory molecules in response to ultraviolet (UV) radiation and other damage. These cytokines recruit and activate members of the innate immune system, including macrophages, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs). Endothelial cells also recruit cells from the innate immune system through adhesion molecules and glycosaminoglycans (GAGs). Endogenous DNA from apoptosis and neutrophil extracellular traps enhance cytokine production by pDCs. pDCs produce interferon (IFN)-α, which recruits members of the adaptive immune system, including Th1 and cytotoxic T cells (CTLs). Th1 cells produce IFN-γ that activates macrophages and CTLs and upregulates its own production. CTLs prime KCs and other cells for apoptosis through granzyme B (GrB), which activates caspases in the target cells. KCs recruit invariant natural killer T cells (iNKTs) through enhanced expression of the antigen-presenting molecule CD1d. iNKTs produce IFN-γ among other cytokines. Various immune cells promote differentiation and activity of Th17 cells through the production of IL-6. Th17 cells produce IL-17. Activity of these cells and cytokines lead to lesion formation and perpetuation characteristic of cutaneous lupus erythematosus. MMP, matrix metalloproteinase; TLR, Toll-like receptor