Infiltrating cells, related cytokines and chemokine receptors in lesional skin of patients with dermatomyositis
- PMID: 15491417
- DOI: 10.1111/j.1365-2133.2004.06144.x
Infiltrating cells, related cytokines and chemokine receptors in lesional skin of patients with dermatomyositis
Abstract
Background: There have been only two reports on immunophenotypic characterization in the cutaneous lesions of dermatomyositis (DM) that emphasize the importance of the infiltrating CD4+ T lymphocytes.
Objectives: To characterize the immunophenotype of the cells that infiltrate the lesional skin of DM and to evaluate the possible T-helper (Th) polarization Th1/Th2 through detection of specific cytokines, chemokine receptors and markers of cellular activation.
Methods: Skin biopsy specimens derived from pathognomonic lesions (Gottron's papules and Gottron's sign) of eight patients with DM were immunostained with a large panel of monoclonal antibodies to CD3, CD4, CD8, myeloperoxidase (MPO), eosinophil cationic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)-2, IL-4, IL-5, IL-13, interferon-gamma, tumour necrosis factor-alpha, receptor 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alkaline phosphatase-antialkaline phosphatase method. Control specimens were obtained from five healthy subjects and from six patients with discoid lupus erythematosus.
Results: Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was approximately 2.5. A mixed Th1/Th2 profile and higher Th1 cytokine production together with significant staining for CXCR3 were detected. Neutrophil granulocytes were the second most abundant population; eosinophil granulocytes were very poorly represented.
Conclusions: Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction between CD40 and CD40L could be an important mechanism of cellular activation in cutaneous immune-mediated inflammation by induction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. There was a significant quantity of MPO+ cells (neutrophil granulocytes) in the inflamed tissue, and they might have a role in sustaining the chronic inflammation.
Comment in
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Evidence for a role of type I interferons in the pathogenesis of dermatomyositis.Br J Dermatol. 2005 Aug;153(2):462-3; author reply 463-4. doi: 10.1111/j.1365-2133.2005.06786.x. Br J Dermatol. 2005. PMID: 16086781 No abstract available.
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