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Steffen, Sabine; Abraham, Susanne; Herbig, Maik; Schmidt, Franziska; Blau, Kristin; Meisterfeld, Susann; Beissert, Stefan; Guck, Jochen; Günther, Claudia
Journal of investigative dermatology, February 2018, 2018-02-00, 20180201, Letnik: 138, Številka: 2Journal Article
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 1/2, 2/6, or 7, but not 7/8, resulted in enhanced surface expression and secretion of CXC chemokine ligand (CXCL) 16. The corresponding CXC chemokine receptor 6 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 tumor necrosis factor−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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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