Role of the Chemokine Receptor CCR4 and its Ligand Thymus- and Activation- Regulated Chemokine/CCL17 for Lymphocyte Recruitment in Cutaneous Lupus Erythematosus

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Presentation transcript:

Role of the Chemokine Receptor CCR4 and its Ligand Thymus- and Activation- Regulated Chemokine/CCL17 for Lymphocyte Recruitment in Cutaneous Lupus Erythematosus Joerg Wenzel, Stephanie Henze, Eva Wörenkämper, Etiena Basner-Tschakarjan, Malgorzata Sokolowska-Wojdylo, Julia Steitz, Thomas Bieber, Thomas Tüting Journal of Investigative Dermatology Volume 124, Issue 6, Pages 1241-1248 (June 2005) DOI: 10.1111/j.0022-202X.2005.23755.x Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Immunohistological analyses of CD3, CD4, CD8, cutaneous lymphocyte antigen (CLA), CC receptor (CCR)4, and granzyme B expression. Lesional skin biopsies were taken from patients with localized chronic discoid lupus erythematosus (lCDLE) (n=5), disseminated CDLE (dCDLE) (n=4), subacute cutaneous LE (SCLE) (n=11), systemic LE (SLE) (n=5), and healthy controls (n=5). Stainings were performed using the LSAB2 kit. Sections were analyzed by two experienced dermatohistopathologists independently. Expression was evaluated as cells per high-power field (× 200 magnification). One point in the figure represents the mean results of the two investigators. Journal of Investigative Dermatology 2005 124, 1241-1248DOI: (10.1111/j.0022-202X.2005.23755.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Representative clinical and immunohistochemical findings in a patient suffering from scarring discoid lupus erythematosus (LE). Clinical investigation revealed scarring disseminated erythematosquamous plaques (a, b). Skin lesions were immunohistologically characterized by a dense junctional and perivascular lymphocytic infiltrate primarily composed of T cells, with a slight majority of CD4+ T cells (c) over CD8+ T cells (d). Furthermore, a high expression of cutaneous lymphocyte antigen (CLA) (e), CC receptor (CCR)4 (f), and granzyme B (g) was found (original magnification: × 200). Immunofluorescence double staining for CD8 (fluorescein isothiocyanate, green) and CCR4 (TRITC, red) revealed the presence of CCR4-expressing CD8+ T cells (yellow, →) in the upper dermis (h; original magnification: × 400). Journal of Investigative Dermatology 2005 124, 1241-1248DOI: (10.1111/j.0022-202X.2005.23755.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Representative clinical and immunohistochemical findings in a patient suffering from scarring discoid lupus erythematosus (LE). Clinical investigation revealed scarring disseminated erythematosquamous plaques (a, b). Skin lesions were immunohistologically characterized by a dense junctional and perivascular lymphocytic infiltrate primarily composed of T cells, with a slight majority of CD4+ T cells (c) over CD8+ T cells (d). Furthermore, a high expression of cutaneous lymphocyte antigen (CLA) (e), CC receptor (CCR)4 (f), and granzyme B (g) was found (original magnification: × 200). Immunofluorescence double staining for CD8 (fluorescein isothiocyanate, green) and CCR4 (TRITC, red) revealed the presence of CCR4-expressing CD8+ T cells (yellow, →) in the upper dermis (h; original magnification: × 400). Journal of Investigative Dermatology 2005 124, 1241-1248DOI: (10.1111/j.0022-202X.2005.23755.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Flow cytometric analyses of cutaneous lymphocyte antigen (CLA) and CC receptor (CCR)4 expression. Flow cytometric analyses of CLA and CCR4 were performed on lymphocytes isolated from peripheral blood of lupus erythematosus (LE) patients (localized chronic discoid LE (lCDLE) (n=5); disseminated CDLE (dCDLE) (n=4); subacute cutaneous LE (SCLE) (n=11); systemic LE (SLE) (n=5)); and controls (healthy volunteers (n=5); psoriasis (n=5); zoster (n=5)). The mean percent of CD4+ or CD8+ T lymphocytes expressing the indicated molecules±SEM are shown (*p<0.05; **p<0.01; ns=not significant when compared with healthy controls). Journal of Investigative Dermatology 2005 124, 1241-1248DOI: (10.1111/j.0022-202X.2005.23755.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Representative findings of cutaneous lymphocyte antigen (CLA) and CC receptor (CCR)4 expression on CD8+ T cells. Typical flow cytometric findings of peripheral blood lymphocytes of a patient suffering from disseminated chronic discoid lupus erythematosus (dCDLE) and a healthy volunteer are depicted. Numbers represent the percentage of CD8+ T cells coexpressing CLA+ or CCR4+. Journal of Investigative Dermatology 2005 124, 1241-1248DOI: (10.1111/j.0022-202X.2005.23755.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Thymus- and activation regulated chemokine (TARC/CCL17) expression in the skin and serum. The expression of TARC/CCL17 in skin and serum was analyzed by immunohistochemistry and ELISA, respectively. In cutaneous lupus erythematous (CLE) lesions, strong TARC/CCL17 expression (red) was detectable in the epidermis and in perivascular areas in all investigated subsets (a). (b) Representative immunohistological findings in a patient with disseminated chronic discoid lupus erythematosus (dCDLE). Serum analyses by ELISA revealed significantly elevated TARC/CCL17 serum levels in all investigated LE subsets when compared with healthy controls (c). Mean levels±SEM are depicted. Journal of Investigative Dermatology 2005 124, 1241-1248DOI: (10.1111/j.0022-202X.2005.23755.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Thymus- and activation regulated chemokine (TARC/CCL17)-directed migration of CD4+ and CD8+ T lymphocytes. The functional relevance of chemokine receptor (CCR)4 expression found on T lymphocytes isolated from peripheral blood of disseminated chronic discoid lupus erythematosus (dCDLE) patients was investigated by an in vitro chemotactic migration assay. Migration was evaluated by determining the chemotactic index (specifically migrated cells divided by unspecifically migrated cells). Results revealed significant migration of peripheral CD4+ CCR4+ and CD8+ CCR4+ lymphocytes from dCDLE patients at an optimal TARC/CCL17 concentration of 40 ng per mL when compared with healthy controls (p<0.01). mean levels of the chemotactic index±SEM are depicted. Journal of Investigative Dermatology 2005 124, 1241-1248DOI: (10.1111/j.0022-202X.2005.23755.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions