Glucocorticoid-induced tumour necrosis factor receptor (GITR) and its ligand (GITRL) in atopic dermatitis.
The glucocorticoid-induced tumour necrosis factor receptor-related gene (GITR) is expressed on regulatory T-cells (Treg), which are CD4+CD25+ lymphocytes. Binding of the GITR-ligand (GITRL) leads to downregulation of the regulatory function of Tregs. Patients suffering from a defect in their Tregs exhibit a condition in their skin resembling atopic dermatitis. GITR also exists in a soluble form, and increased levels of this lead to decreased levels of GITRL and thereby increased Treg activity. We have measured the levels of GITR and GITRL in plasma from atopic dermatitis patients and found it not to be increased. Furthermore, plasma levels of GITR and GITRL did not correlate with SCORAD. Both GITR and GITRL correlated with the levels of thymus- and activation-regulated chemokine/CCL17 and cutaneous T-cell-attracting chemokine/CCL27, two chemokines believed to play a major role in the pathogenesis of atopic dermatitis and the migration of Tregs and skin-homing T-cells. Immunohistochemistry showed GITR and GITRL were present in few dermal cells of both patients with atopic dermatitis, and normal healthy volunteers, and often localized in close proximity to each other. Since regulatory T-cells are localized in the vicinity of GITRL-expressing cells in atopic dermatitis skin, the GITR/GITRL interaction may serve to perpetuate the inflammation locally.
Baumgartner-Nielsen
Jane
J
Department of Dermatology, Aarhus University Hospital, P.P Oerumsgade 11, DK-8000 Aarhus C, Denmark. jaban@as.aaa.dk
Vestergaard
Christian
C
Thestrup-Pedersen
Kristian
K
Deleuran
Mette
M
Deleuran
Bent
B
D000293:Adolescent; D000328:Adult; D054414:Chemokine CCL17; D054425:Chemokine CCL27; D019742:Chemokines, CC / Q000097:blood; D003876:Dermatitis, Atopic / Q000503:physiopathology*; D020405:Dermis / Q000378:metabolism; D005260:Female; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D008297:Male; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000378:metabolism*
C106230:CCL17 protein, human; C492276:CCL27 protein, human; D054414:Chemokine CCL17; D054425:Chemokine CCL27; D019742:Chemokines, CC; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; C478967:TNFSF18 protein, human; D048069:Tumor Necrosis Factors