Antigen-specific induction of osteopontin contributes to the chronification of allergic contact dermatitis.
Allergic contact dermatitis is a T cell-mediated immune response, which in its relapsing chronic form is of high socioeconomic impact. The phosphoglycoprotein osteopontin (OPN) has chemotactic and Th1 cytokine functions and in various models is essential for robust T cell-mediated immunity. Here we demonstrate that OPN is abundantly expressed by both effector T cells and keratinocytes in allergic contact dermatitis lesions. T cells from nickel-allergic donors secrete high levels of OPN following antigen-specific stimulation. OPN may substitute for missing IFN-gamma secretion in T effector cells because low IFN-gamma-producing T cell clones secrete high levels of OPN, and OPN down-modulates their interleukin-4 expression. Furthermore, interferon-gamma from T effector cells augments OPN in allergic contact dermatitis by inducing OPN in keratinocytes, which in turn polarizes dendritic cells and attracts inflammatory cells. In the murine contact hypersensitivity (CHS) model for allergic contact dermatitis, OPN is strongly induced in antigen-specific proliferating T cells, and OPN null mice display a reduced chronic CHS inflammatory response due to a decreased influx of effector T cells. Importantly, because of its function for chronic allergic contact dermatitis, OPN may well be a therapeutic target, because anti-OPN antibody treatment in part suppresses established chronic CHS.
Seier
Anne M
AM
Department of Dermatology and Allergology, University of Ulm, Ulm 89081, Germany.
Renkl
Andreas C
AC
Schulz
Guido
G
Uebele
Tanja
T
Sindrilaru
Anca
A
Iben
Sebastian
S
Liaw
Lucy
L
Kon
Shigeyuki
S
Uede
Toshimitsu
T
Weiss
Johannes M
JM
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D002999:Clone Cells; D017449:Dermatitis, Allergic Contact / Q000097:blood / Q000276:immunology* / Q000473:pathology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D018448:Models, Immunological; D009532:Nickel / Q000009:adverse effects / Q000276:immunology*; D053495:Osteopontin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism; D014019:Tissue Donors
D000906:Antibodies; D000939:Epitopes; D011971:Receptors, Immunologic; D053495:Osteopontin; D009532:Nickel; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens