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

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-gamma-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 compartmentalized 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+2, CD11b+2). 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-gamma-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.

Alternative activation deprives macrophages of a coordinated defense program to Mycobacterium tuberculosis

“…The MMR has been used to identify murine alternatively activated macrophages [24]; however, since M. tuberculosis infection down-regulates surface expression of MMR, additional markers are required. Here, we identified MMP-12 as characteristic marker of alternative activation of macrophages, consistent with a functional involvement of alternatively activated macrophages and MMP in wound healing processes [79,80].…”

Misbehaving macrophages in the pathogenesis of psoriasis

“…Macrophages contribute to psoriasis in 2 mouse models Infiltration of macrophages, especially around the epidermal/dermal interface, is a well-established feature of human psoriasis, but the contribution of these cells to psoriatic inflammation was previously unknown (14)(15)(16)(17)(18)(19). In this issue, Wang et al (20) and Stratis et al (12) address for the first time to our knowledge the importance of macrophages in mouse models of psoriasis.…”

Paucity of FOXP3+ cells in skin and peripheral blood distinguishes Sézary syndrome from other cutaneous T-cell lymphomas

“…15 All specimens were blinded and analyzed by two independent investigators (CDK, NP) as described. 16 Each investigator evaluated the proportion of positively stained cells, expressed as a fraction of the total lymphocytic infiltrate, and the percentage of CD4 þ and FOXP3 þ cells for each case was calculated from the values of six different areas.…”