Abstract
Objective and designThe aim of this study was to elucidate the role of apoptosis mediated through Fas/FasL pathway using the mouse model of atopic dermatitis (AD).Materials and treatment AD was induced by epicutaneous application of ovalbumin (OVA) in wild-type C57BL/6, B6. MRL-Faslpr/J (Fas−) and B6Smn.C3-Faslgld/J (FasL−) mouse strains.MethodsSkin samples were subjected to staining for Fas/FasL expression, M30 epitope and assessment of inflammatory response via immunohistochemical staining. Cytokine and chemokine production was assessed by real-time PCR.ResultsIn comparison to wild-type mice, OVA sensitization of Fas- and FasL-deficient mice led to increased epidermal and dermal thickness, collagen deposition and local inflammation consisting of macrophages, neutrophils and CD4+ T cells. Fas- and FasL-deficient mice showed increased total counts of regulatory T cells (Tregs) and IgE levels in blood as well as increased expression of IL-1β, IL-4, IL-5, IL-13 and TGF-1β mRNA in comparison to wild-type mice. On the other hand, expression of CXCL9 and CXCL10, IL-17 mRNAs in the skin samples in Fas- and FasL-deficient mice was decreased.ConclusionsOur results show that lack of the Fas-induced apoptosis leads to exacerbation of AD characteristics such as Th2 inflammation and dermal thickening. Therefore, Fas receptor can play an important role in AD pathogenesis by controlling development of the local inflammation.
Highlights
Atopic dermatitis (AD) is a common allergic skin disorder characterized by chronic relapsing form of skin inflammation, disturbance of epidermal barrier function that leads to dry skin, and keratinocyte apoptosis as a mechanism of eczema and spongiosis formation, which is mostly seen in acute and subacute lesions
Since epidermal keratinocytes express Fas in low amounts [8] and FasL expression is detected in the inflammatory skin conditions [10], first we accessed Fas and FasL expression in the skin of mice subjected to ovalbumin (OVA) or saline epicutaneous sensitization (EC) (Fig. 1a)
In vitro studies using cells isolated from patients with atopic dermatitis (AD) have shown that T cells induce the expression of Fas on keratinocytes [3]
Summary
Atopic dermatitis (AD) is a common allergic skin disorder characterized by chronic relapsing form of skin inflammation, disturbance of epidermal barrier function that leads to dry skin, and keratinocyte apoptosis as a mechanism of eczema and spongiosis formation, which is mostly seen in acute and subacute lesions. The pathogenesis of AD is multifactorial including genetic, environmental, skin barrier, psychological and immunological factors [1, 2]. During AD, the local response of keratinocytes together with the reaction of endothelial cells, T cells, mast cells, macrophages, eosinophils and dendritic cells leads to the characteristic clinical and histological appearance of AD [1, 2]. Genetically controlled process, which can be triggered by a variety of extrinsic and intrinsic signals [5].
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