Role of the chemokine receptor CCR4 and its ligand thymus- and activation-regulated chemokine/CCL17 for lymphocyte recruitment in cutaneous lupus erythematosus.
Skin-infiltrating T lymphocytes are thought to play a major role in the pathogenesis of cutaneous lupus erythematosus (CLE). In this study, we investigated the role of the chemokine receptor 4 (CCR4) and its ligand thymus- and activation-regulated chemokine (TARC/CCL17) for the recruitment of T cells in inflamed skin of patients with CLE. We found significant numbers of CCR4+ T lymphocytes in the skin of all patients with CLE. Interestingly, a subset of patients with disseminated scarring skin involvement were characterized by both lesional and circulating CD8+ T cells expressing CCR4. Destruction of epidermal and adnexal structures was histomorphologically associated with CCR4+ cytotoxic T cells invading basal layers of the epidermis where keratinocytes showed apoptotic death. The CCR4 ligand TARC/CCL17 was strongly expressed in skin lesions and elevated in the serum of CLE patients. The functional relevance of lymphocytic CCR4 expression could be confirmed by TARC/CCL17-specific in vitro migration assays. Our investigations suggest that CCR4 and TARC/CCL17 play a role in the pathophysiology of CLE. In particular, cytotoxic CD8+ T cells expressing CCR4 appear to be involved in scarring subtypes of CLE.
Wenzel
Joerg
J
Department of Dermatology, University of Bonn, Bonn, Germany. joerg.wenzel@ukb.uni-bonn.de
Henze
Stephanie
S
Wörenkämper
Eva
E
Basner-Tschakarjan
Etiena
E
Sokolowska-Wojdylo
Malgorzata
M
Steitz
Julia
J
Bieber
Thomas
T
Tüting
Thomas
T
D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002465:Cell Movement; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000097:blood / Q000378:metabolism*; D002921:Cicatrix / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D008024:Ligands; D008178:Lupus Erythematosus, Cutaneous / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D008179:Lupus Erythematosus, Discoid / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism*; D012867:Skin / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C106230:CCL17 protein, human; C515354:CCR4 protein, human; C063419:CTAGE1 protein, human; D054414:Chemokine CCL17; D019742:Chemokines, CC; D008024:Ligands; D008562:Membrane Glycoproteins; D054398:Receptors, CCR4; D019707:Receptors, Chemokine