Expression of the C-C chemokine MIP-3 alpha/CCL20 in human epidermis with impaired permeability barrier function.
External assault to the skin is followed by an epidermal response including synthesis of DNA, lipids, cytokines and migration of antigen presenting cells. MIP-3 alpha (CCL20, LARC, Exodus-1, Scya20) is a recently described C-C chemokine, predominantly expressed in extralymphoid tissue, which is known to direct migration of dendritic cell precursors and memory lymphocytes to sites of antigen invasion. We assessed the expression of MIP-3 alpha in human skin using semi-quantitative polymerase chain reaction. In vivo, MIP-3 alpha mRNA was constitutively expressed at low levels in untreated human epidermis. After acute disruption of the epidermal permeability barrier MIP-3 alpha mRNA was upregulated in the epidermal fraction, whereas dermal MIP-3 alpha mRNA levels remained unchanged. In vitro, MIP-3 alpha was increased in cultured keratinocytes treated with IL-1 alpha and TNF-alpha and was present in immature and mature dendritic cells, THP-1 monocytic cells and activated T cells. Finally, skin biopsies from patients with psoriasis, contact dermatitis and mycosis fungoides showed abundant expression. In biopsies from atopic dermatitis and graft vs. host disease a weak signal was present, whereas no expression was found in scleroderma and toxic epidermal necrolysis. We conclude that regulation of MIP-3 alpha mRNA is part of the epidermal response to external assault. Its upregulation may represent a danger signal for increased immunosurveillance in barrier disrupted skin and inflammatory skin conditions with impaired barrier function to counteract potential antigen invasion.
Schmuth
M
M
Departments of Dermatology, University of Innsbruck, Innsbruck, Austria. matthias.schmuth@uibk.ac.at
Neyer
S
S
Rainer
C
C
Grassegger
A
A
Fritsch
P
P
Romani
N
N
Heufler
C
C
D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D012867:Skin / Q000378:metabolism; D012871:Skin Diseases / Q000378:metabolism; D015854:Up-Regulation
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine