Productive role of fractalkine and CXCL16 in human epidermal keratinocytes

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CXCL16 is a ligand for CXCR6, a CXC-chemokine receptor. CXCL16 is synthesized as a membrane-bound form that is cleaved to a soluble form that is a chemoattractant for CXCR6-expressing cells such as activated CD8 T cells, NKT cells, and Th1-polarized CD4 and CD8 T cells. By contrast, a membrane-bound form of CXCL16 expressed on human macrophages and dendritic cells acts as a scavenger receptor for oxidized low density lipoprotein. In addition, CXCL16 expressed on macrophages mediates adhesion and phagocytosis of bacteria such as Escheria coli or Staphylococcus aureus. The soluble chemokine domain of CXCL16 at concentrations > 5 □g/ml had antimicrobial activity against S.aureus and E.coli. Addition of 10 □g/ml soluble CXCL16 reduced the survival rate of S.aureus and E.coli by 70 and 40%, respectively. Because CXCL16 is produced constitutively by HEK, CXCL16 contributes to host-defense function in relation to microbial pathogens in human skin as well as □-defensins.Fractalkine/CX3CL1, a chemokine, is synthesized as a membrane bound form and converted to a soluble form by protease(s). Since fractalkine recruits CX3CR1 positive cells such as NK cells and CD8+ T cells, it is supposed to be involved in recruiting these cells into the epidermis in the inflammatory reaction. To address this issue, we investigated whether normal human keratinocytes can produce fractalkine in the presence of cytokines. TNF-□, IL1-□□ and IFN-□ synergistically enhanced IFN-□-induced fractalkine production in normal human keratinocytes. In conclusion, this is the first report showing that normal human keratinocytes produce soluble fractalkine protein.