The role of Toll-like receptors in skin diseases

The innate immune system has the ability to recognize pathogens through Toll-like receptors (TLRs), which are transmembrane glycoproteins on the cell surface. These receptors present on the surface of immunological cells – macrophages, dendritic cells, mast cells and some populations of lymphocytes – play an important role in the defense against bacterial, viral and fungal infections. The connection of a Toll-like receptor with the microbial cell component known as pathogen associated molecular pattern (PAMP) induces intracellular mechanisms leading to the synthesis of proinflammatory cytokines. Depending on the kind of the recognized ligand, TLRs are classified into subfamilies. So far, 13 TLRs have been described in mice and 11 in humans. These receptors may be expressed extracellularly (TLRs 1, 2, 4, 5, 6, 10, 11) or intracellularly, located in endosomes (TLRs 3, 7, 8, 9). Recent studies also indicate their role in the development of many dermatoses. Occurrence of these receptors has been found on the surface of epidermal and dermal cells: keratinocytes, Langerhans cells, fibroblasts, endo-thelial cells, melanocytes and adipocytes. This paper presents the structure and function of Toll-like receptors and their role in the pathogenesis of some infectious skin diseases, autoimmune and allergic dermatoses as well as skin neoplasms. The knowledge about the role of Toll-like receptors in the development of skin diseases creates the possibility to use them in treatment in the future

CD4<sup>+</sup>CD25<sup>+</sup> and CD4<sup>+</sup>CD25high regulatory T cells in disseminated and localized forms of allergic contact dermatitis: relation to specific cytokines

The aim of this study was to evaluate regulatory T lymphocytes (Tregs) in the course of allergic contact dermatitis (ACD) and to elucidate the role of IL-10 and TGF-b in Tregs activity. Peripheral blood CD4<sup>+</sup>CD25<sup>+</sup> and CD4<sup>+</sup>CD25<sup>high</sup> cells were determined by flow cytometry in patients with acute disseminated ACD (‘ad’, n = 36), acute localized ACD (‘al’, n = 26), and disseminated ACD during remission (‘rd’, n = 27) as well as in controls (n = 22). Serum levels of cytokines were measured using ELISA. The mean percentage of CD4<sup>+</sup>CD25<sup>+</sup> and CD4<sup>+</sup>CD25<sup>high</sup> cells in patients with ad ACD was significantly higher than in controls (p < 0.01) and the remaining patients (p < 0.05). Both cell populations were significantly elevated in persons with widespread skin lesions (p < 0.05). In ad patients the CD4<sup>+</sup>CD25<sup>+</sup> increased during three weeks of disease, although the significant increase of CD4<sup>+</sup>CD25<sup>high</sup> was noted only in the third week. Patients with ad ACD showed a significantly decreased serum level of TGF-<i>b</i>1 as compared with controls and the remaining ACD patients. IL-10 level did not differ between all groups. The elevated population of CD4<sup>+</sup>CD25<sup>high</sup> cells in ad ACD patients, and its dependence on the extension of skin lesions, suggest a role of Tregs in regulating the course of ACD. The growing Tregs percentages may indicate their peripheral generation during ACD. The development of lesions despite an increased population of Tregs suggests their functional defect. The role of TGF-<i>b</i>1 in the suppressive activity of Tregs cannot be excluded. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 255–262

CD4+CD25+ and CD4+CD25high regulatory T cells in disseminated and localized forms of allergic contact dermatitis: relation to specific cytokines

The aim of this study was to evaluate regulatory T lymphocytes (Tregs) in the course of allergiccontact dermatitis (ACD) and to elucidate the role of IL-10 and TGF-b in Tregs activity. Peripheral bloodCD4+CD25+ and CD4+CD25high cells were determined by flow cytometry in patients with acute disseminatedACD (‘ad’, n = 36), acute localized ACD (‘al’, n = 26), and disseminated ACD during remission (‘rd’, n = 27)as well as in controls (n = 22). Serum levels of cytokines were measured using ELISA. The mean percentage ofCD4+CD25+ and CD4+CD25high cells in patients with ad ACD was significantly higher than in controls(p < 0.01) and the remaining patients (p < 0.05). Both cell populations were significantly elevated in personswith widespread skin lesions (p < 0.05). In ad patients the CD4+CD25+ increased during three weeks ofdisease, although the significant increase of CD4+CD25high was noted only in the third week. Patients with adACD showed a significantly decreased serum level of TGF-b1 as compared with controls and the remainingACD patients. IL-10 level did not differ between all groups. The elevated population of CD4+CD25high cells inad ACD patients, and its dependence on the extension of skin lesions, suggest a role of Tregs in regulating thecourse of ACD. The growing Tregs percentages may indicate their peripheral generation during ACD. Thedevelopment of lesions despite an increased population of Tregs suggests their functional defect. The role ofTGF-b1 in the suppressive activity of Tregs cannot be excluded

Patch test results in children and adolescents suffering from allergic contact dermatitis – comparison of patients with and without atopic dermatitis

Introduction . Allergic contact dermatitis is a more and more frequently diagnosed skin disease in children and adolescents. It may coexist with atopic dermatitis. The frequency of allergy to certain contact haptens is determined by numerous factors. Objective. To assess the frequency of allergy to selected contact allergens among children and adolescents with symptoms of contact eczema. Material and methods . Two hundred seventy-three consecutive patients aged 4–18 years treated because of allergic contact eczema were included in this study. The demographic data and patch test results were assessed in the total group and separately in two age groups of patients without and with atopic dermatitis. Results . The total group examined included 71 (44 female and 27 male) children and 202 (145 female and 57 male) adolescents. Atopic dermatitis was diagnosed in 64 patients. The patch test results were positive in 36.3% of examined subjects: 26.5% of children and 39.6% of adolescents, with a similar frequency in patients with and without atopic dermatitis. The most common contact sensitizers were nickel sulfate (20.1%), cobalt chloride (12.8%), p-phenylenediamine (3.3%), potassium dichromate and fragrances (2.9% each), balsam of Peru and neomycin sulfate (1.5% each). Cobalt, chromate, fragrances and balsam of Peru more frequently sensitized patients with atopic dermatitis. Among the younger boys with atopic dermatitis there were no cases of contact allergy to nickel and cobalt, while in the atopic adolescent males the results with each of these allergens were positive in 20% of those examined. Conclusions . Contact allergy is detected similarly frequent in children and adolescents with and without atopic dermatitis. The very high prevalence of allergy to nickel and cobalt is a significant problem among teenage girls and boys with atopic dermatitis

Osteopontin and Regulatory T Cells in Effector Phase of Allergic Contact Dermatitis

Studies have shown that osteopontin (OPN) and regulatory T cells play a role in allergic contact dermatitis (ACD), but the mechanisms responsible for their function are poorly understood. The study aimed to determine CD4 T lymphocytes producing intracellular osteopontin (iOPN T cells) and assess the selected T lymphocyte subsets including regulatory T cells in the blood of patients with ACD. Twenty-six patients with a disseminated form of allergic contact dermatitis and 21 healthy controls were enrolled in the study. Blood samples were taken twice: in the acute phase of the disease and during remission. The samples were analyzed by the flow cytometry method. Patients with acute ACD showed significantly higher percentage of iOPN T cells compared with healthy controls which persisted during remission. An increase in the percentage of CD4CD25 and a reduced percentage of regulatory T lymphocytes (CD4CD25highCD127low) were also found in the patients with acute stage of ACD. The percentage of CD4CD25 T lymphocytes showed a positive correlation with the EASI index. The increase in the iOPN T cells can indicate their participation in acute ACD. The decreased percentage of regulatory T lymphocytes in the acute stage of ACD may be related to the transformation of Tregs into CD4CD25 T cells. It may also indicate their increased recruitment to the skin. The positive correlation between the percentage of CD4CD25 lymphocytes and the EASI index may be indirect evidence for the importance of activated lymphocytes—CD4CD25 in addition to CD8 lymphocytes as effector cells in ACD