3 years ago

Toll-like receptor-mediated upregulation of CXCL16 in psoriasis orchestrates neutrophil activation.

Beissert, Herbig, Meisterfeld, Günther, Abraham, Steffen, Guck, Schmidt, Blau
Innate immune processes are central in the development of the chronic inflammatory skin disease psoriasis. Studying stimulation of keratinocytes, monocytes and dendritic cells by type I interferons or ligation of toll-like receptors TLR1/2, TLR2/6 or TLR7, but not TLR7/8, resulted in enhanced surface expression and secretion of the chemokine CXCL16. The corresponding receptor CXCR6 was expressed on neutrophils whose recruitment into skin is important especially in early psoriatic disease. Using the recently developed technique real-time deformability cytometry demonstrated that CXCL16 and IL-8 decreased the stiffness and enhanced deformation of neutrophils facilitating transmigration through vessel wall. In addition, CXCL16 potently induced migration of neutrophils and enhanced the chemotactic effect of IL-8. The positive feedback loop was supported by IL-8 enhancing CXCL16 production of neutrophils. Blocking of CXCL16 expression by effective treatment of psoriasis patients with TNF-α blockers further supported the pathogenic role of this chemokine. In summary, the data link innate immune stimulation to CXCL16 upregulation and neutrophil infiltration into skin. CXCL16 could therefore represent a potent future target for treatment of psoriasis.

Publisher URL: http://doi.org/10.1016/j.jid.2017.08.041

DOI: 10.1016/j.jid.2017.08.041

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