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CXCL16 and CXCR6 are upregulated in psoriasis and mediate cutaneous recruitment of human CD8+ T cells.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2012 Mar; Vol. 132 (3 Pt 1), pp. 626-34. Date of Electronic Publication: 2011 Nov 24. - Publication Year :
- 2012
-
Abstract
- Psoriatic skin lesions are characterized by an inflammatory infiltrate, consisting of dendritic cells, monocytes, and both CD4(+) and CD8(+) T lymphocytes. Although the chemokines involved in the migration of CD4(+) T cells into psoriatic skin are well characterized, those regulating CD8(+) T-cell recruitment are less understood. We found that the percentages of peripheral blood CD8(+) T cells expressing CXCR6 were higher in psoriatic patients than in healthy or atopic individuals. In addition, CXCR6 expression in psoriatic patients was more abundant in the CD8(+) than in the CD4(+) T-cell compartment. CXCR6 mRNA expression was also stronger in skin CD8(+) T cells than in the corresponding blood-derived counterparts. Immunofluorescence analysis revealed profound upregulation of the CXCR6 ligand CXCL16 by monocytes, keratinocytes, and dendritic cells in psoriatic skin compared with healthy or atopic dermatitis skin. In line with this, CXCR6(+) CD8(+) T cells also were most prevalent in psoriatic skin. Furthermore, CXCL16 induced Ca(2+) influx and chemotactic migration of psoriatic skin-derived CD8(+) T cells in vitro. Most importantly, CXCL16 potently recruited human CD8(+) T cells to human skin grafts previously transplanted onto SCID mice in vivo. These investigations indicate that CXCL16-CXCR6 interactions mediate homing of CD8(+) T cells into human skin, and thereby contribute to psoriasis pathogenesis.
- Subjects :
- Animals
CD3 Complex immunology
Calcium metabolism
Cell Movement immunology
Cells, Cultured
Chemokine CXCL16
Dendritic Cells immunology
Dermatitis, Atopic immunology
Humans
Keratinocytes immunology
Mice
Mice, SCID
Monocytes immunology
Receptors, CCR4 immunology
Receptors, CCR7 immunology
Receptors, CXCR6
Skin immunology
Up-Regulation immunology
CD8-Positive T-Lymphocytes immunology
Chemokines, CXC immunology
Psoriasis immunology
Receptors, Chemokine immunology
Receptors, Scavenger immunology
Receptors, Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 132
- Issue :
- 3 Pt 1
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 22113484
- Full Text :
- https://doi.org/10.1038/jid.2011.371