Role of innate immunity and microbial component in the skin and pathogenesis of psoriasis
AbstractBackground The origin of dermatitis at patients with psoriasis testifies to the available activated state of epidermis and derm a cells that along with other factors may be stipulated by participation of Toll-like receptors. The increase in expression of TLR2 and TLR4 in epidermis and inflammatory infiltrate of derm a at patients with psoriasis points out to the possibility for its interaction with bacterial factor. However, there are no papers in the modern literature that are devoted to research on expression of Toll-like receptors providing that there are persistent microorganisms in the skin.Objectives. The objectives of our paper were to study the character and prevalence of local cellular immune and inflammatory reactions in sites of dermal psoriaform and sites of intact skin at patients with psoriasis using the immunohistochemical methods with definition of TLR2, TLR4 expression markers, as well as availability and species composition of microorganisms’ colonies.Methods. We performed the pathomorphological and immunohistochemical research of biopsic material, taken from sites of dermal psoriaform and intact skin at patients with psoriasis, before and after immune suppressive therapy by etanercept during 3 months.Results. The close contact of TLR2-positive macrophages is observed in the subepithelial sites with positively colored dendritic cells of epidermis, thereby, the expression of marker in these areas was observed in epithelial cells across the whole width of the layer up to the horny layer. The mentioned structural peculiarities may testify to activation of macrophages by dendritic cells of epidermis, which bind and concentrate the corresponding ligands. The analogous changes were found at study of TLR4 expression. The significant amount of TLR4 – positive dendritic cells, which had considerably larger sizes and were spread with their appendices up to the horny layer, was found in epidermis even after performed treatment. Hereby rather intensive background cytoplasmic coloration of those cells was observed. It should be mentioned that the colonies of microorganisms were observed in the horny scales of the skin. The scales of horny substance at patients with psoriasis have the soft layer-by-layer structure that establishes the conditions for their colonization by a great number of microorganisms, which waste products may act as ligands in activation of Toll-like receptors. The results from immunohistochemical research es of biopsic material, taken from skin sites , affected by dermal psoriaform and sites of intact skin at patients with psoriasis, before and after the course of system immune suppressive therapy point out to the significant importance for expression of Toll-like receptors 2 and 4 (TLR2, TLR4) in development of immune inflammation in the skin providing that there is the microbial component in the corresponding sites.Conclusion. The hyperproduction and hypersecretion of proinflammatory biological markers, in particular, TLR2, 4 – positive cells, by epithelial cells was established at patients with psoriasis. Hereby, the corresponding TLR – positive cells are found both in sites of skin, affected by psoriaform, and in sites of intact skin. TLR2-, TLR4- positive macrophages after their activation in the papilla of derma migrate to the papilla bases, where they are included into composition of inflammatory infiltrates, located perivascularly. The reduction in a number of cells (both dendritic cells and macrophages), in which the expression of TLR2 and TLR4 is found, was established in sites of skin, affected by psoriaform, after performed treatment of patients with psoriasis involving the system immune suppressive therapy. The long term presence of bacterial component in sites of skin, affected by psoriaform, may be one of pathogenetic inciting factors for production of proinflammatory cytokines that assists to support of inflammatory psoriatic process. The expression of TLR – positive cells, established in epidermis and derma at patients with psoriasis, points out that the important link in the pathogenesis of this dermatosis is the antigenic stimulation of immune competent cells, which results in development of inflammatory process in the surface layers of the skin. Further advanced researches on interrelation of staphylococci, persistent in the skin, with factors of innate immunity, namely Toll-like receptors, are perspective in terms of receipt of the newest data about pathogenesis of psoriasis with particularization of innate immunity disorders and proliferative activity of keratinocyte in psoriatic scales.
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