CXCR6 and its ligand CXCL16 preferentially mediate CD8+ T cell recruitment into psoriatic skin
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Guenther, Claudia, Carballido-Perrig, Nicole, Kaesler, Susanne, Carballido, Jose and Biedermann, Tilo (2011) CXCR6 and its ligand CXCL16 preferentially mediate CD8+ T cell recruitment into psoriatic skin. Journal Investigative Dermatology. ISSN 0022-202X
Abstract
Psoriatic skin lesions are characterized by an inflammatory cellular infiltrate, which is recruited by a defined set of chemokines. The most dominant infiltrating cell types are monocytes, CD4+ and CD8+ T cells. Chemokines governing CD4+ T cell recruitment into psoriatic skin are well characterized and include CCR4, CCR6, CCR10, and CXCR3 ligands. In contrast, chemokine-chemokine receptors pairs that regulate recruitment of CD8+ T cells are less well understood. To this end, we studied chemokine receptors on peripheral blood T cells and monocytes and identified CXCR6 as a dominant chemokine receptor on monocytes and CD8+ but not on CD4+ T cells of psoriatic patients. Moreover, CXCR6 mRNA expression was more pronounced in CD8+ T cells from psoriatic skin compared to CD8+ T cells from blood of psoriatic patients and expression levels were higher than for any other chemokine receptor analyzed. Next, CXCR6 and its ligand CXCL16 were analyzed in psoriatic skin by immunofluorescence. CXCL16 was mainly found on cutaneous monocytes, keratinocytes, and dendritic cells and its receptor CXCR6 on T cells and monocytes. Functional consequences were analyzed demonstrating CXCL16 induced Ca2+ influx and migration of skin derived CD8+ T cells in vitro. In vivo, CXCL16 most potently recruited blood derived CD8+ T cells to human skin grafts previously transplanted onto SCID-mice. These investigations indicate that CXCL16 and CXCR6 represent an important ligand-receptor pair mediating CD8+ T cell recruitment in to psoriatic skin.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used |
| Keywords: | Psoriasis, CD8, CXCL16, skin |
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| Date Deposited: | 13 Oct 2015 13:15 |
| Last Modified: | 13 Oct 2015 13:15 |
| URI: | https://oak.novartis.com/id/eprint/4317 |