DNA structures decorated with cathepsin G/secretory leukocyte proteinase inhibitor stimulate IFNI production by plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) and neutrophils are detected in psoriatic skin lesions and implicated in the pathogenesis of psoriasis. pDCs specialize in the production of type I interferon (IFNI), a cytokine that plays an important role in chronic autoimmune-like inflammation, including psoriasis. Here, we demonstrate that IFNI production in pDCs is stimulated by DNA structures containing the neutrophil serine protease cathepsin G (CatG) and the secretory leukocyte protease inhibitor (SLPI), which is a controlling inhibitor of serine proteases. We also demonstrate the presence of neutrophil-derived DNA structures containing CatG and SLPI in lesional skin samples from psoriasis patients. These findings suggest a previously unappreciated role for CatG in psoriasis by linking CatG and its inhibitor SLPI to the IFNI-dependent regulation of immune responses by pDCs in psoriatic skin.