, Volume 288, Issue 12, pp 757-764

Immunohistochemical identification of type II alternatively activated dendritic macrophages (RM 3/1+++, MS-1± 25F9) in psoriatic dermis

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Abstract

Immunological mechanisms play an important role in the pathogenesis of psoriasis. Lesional psoriatic skin-derived T-cell clones have been shown to stimulate keratinocyte proliferation and to predominantly express a T-helper type 1 cytokine pattern. However, T-helper type 2-like cytokines have also been identified in some psoriatic T-cell clones. In parallel to the T-helper type 1/type 2 dichotomy, a distinction between interferon-γ-induced (classically activated) macrophages and interleukin-4/glucocorticoid-induced (alternatively activated) macrophages has been put forward as a conceptual framework for a better understanding of immunopathological processes. In the present study, the phenotype of mononuclear phagocytes in psoriatic skin lesions (n=21), allergic contact dermatitis (n=4) and normal skin (n=2) was investigated using a panel of monoclonal antibodies (mAb) against monocytes/macrophages and dendritic cells (mAb MS-1, RM 3/1 and 25F9 against subsets of in vitro alternatively activated macrophages, and mAb against myeloid antigens CD1a, CD11b, CD11c, CD34, CD36, and CD68). With regard to mononuclear phagocytes, psoriatic skin was found to be compart-mentalized into epidermis, subepidermal space, and upper and lower dermis. RM 3/1+++, MS-1± 25F9 dendritic macrophages previously classified as type II alternatively activated macrophages were the dominant dermal macrophage population in psoriatic skin, while intraepidermal and epithelium-lining macrophages expressed a different, presumably classically activated, macrophage phenotype (RM 3/1, MS-1, 25F9, CD68++, CD11b++). In allergic contact dermatitis a classical T-helper type 1 disease, RM 3/1+++ macrophages were less prominent. Since MS-1 high molecular weight protein is much more sensitive to interferon-γ-induced suppression than RM 3/1 antigen a predominance of T-helper type 1 cytokines in psoriasis could explain why dermal dendritic macrophages do not express the fully induced MS-1+++, RM 3/1+++, 25F9± phenotype of type I alternatively activated macrophages.