[HTML][HTML] CXCL16 and CXCR6 are upregulated in psoriasis and mediate cutaneous recruitment of human CD8+ T cells

C Günther, N Carballido-Perrig, S Kaesler… - Journal of Investigative …, 2012 - Elsevier
C Günther, N Carballido-Perrig, S Kaesler, JM Carballido, T Biedermann
Journal of Investigative Dermatology, 2012Elsevier
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 …
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 Ca2+ 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.
Elsevier