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      T-regulatory cells in severe atopic dermatitis: alterations related to cytokines and other lymphocyte subpopulations

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          Abstract

          The changes in lymphocyte subpopulations in atopic dermatitis (AD) concern also T-regulatory cells. We investigated the expression of various surface receptors on CD3 +CD4 +CD25 highFoxP3 + T-regulatory cells and the activation CD28 + receptor and the inhibitory CD152 + receptor on helper/inducer as well as cytotoxic/suppressor T cells. Peripheral blood lymphocytes of 15 AD patients and 20 healthy subjects were analyzed by flow cytometry using monoclonal antibodies. The concentrations of IL-6, IL-10 and TGF-β were determined in the serum and the supernatant of ConA-stimulated CD4 + lymphocytes. In AD patients the percentage of CD4 +CD25 highFoxP3 + as well as CD3 +CD8 + cells increased, which positively correlated with SCORAD index ( r = 0.55, p = 0.03). The concentrations of IL-10 in the CD4 + lymphocyte culture supernatants and the concentrations of TGF-β in the sera and the supernatant negatively correlated with the severity of AD ( p < 0.01, r = −0.63; p < 0.02, r = −0.64 and p < 0.03, r = −0.58, respectively), whereas the serum concentration of IL-6 correlated positively ( p < 0.003, r = 0.71). The regulatory cells expressed more CD62L and CD134 surface markers but less CD95. Reduced expression of the apoptotic CD95 receptor suggests that survival time of these cells is prolonged. Since CD62L and CD134 were upregulated, the enhanced modulatory effect of CD4 +CD25 highFoxP3 + cells seemed to be suggested, which may result in increased co-expression of CD28/CD152 on both CD4 + and CD8 + subpopulations.

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          Most cited references20

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          Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self.

          Naturally arising CD25(+)CD4(+) regulatory T cells actively maintain immunological self-tolerance. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. A reduction in their number or function can also elicit tumor immunity, whereas their antigen-specific population expansion can establish transplantation tolerance. They are therefore a good target for designing ways to induce or abrogate immunological tolerance to self and non-self antigens.
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            Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis.

            Assessment methods for atopic dermatitis (AD) are not standardized, and therapeutic studies are difficult to interpret. To obtain a consensus on assessment methods in AD and to use a statistical method to develop a composite severity index. Consensus definitions were given for items used in the scoring system (extent, intensity, subjective) and illustrated for intensity items. Slides were reviewed to address within- and between-observer variability by a group of 10 trained clinicians, and data were statistically evaluated with a two-way analysis of variance. Two variants of an assessment system were compared in 88 patients at 5 different institutions. Data were analyzed using principal-component analysis. For 5 intensity items studied (erythema, edema/papulation, oozing/crusts, excoriations, lichenification), within- and between-observer variability was good overall, except for edema/papulation which was difficult to assess with slides. In the series of 88 patients, principal-component analysis allowed to extract two unrelated components: the first one accounting for 33% of total variance was interpreted as a 'severity' component; the second one, accounting for 18% of variance, was interpreted as a 'profile' component distinguishing patients with mostly erythema and subjective symptoms and those with mostly lichenification and dryness and lower subjective symptoms. Of the two evaluation systems used, the one using the rule of nine to assess extent was found more workable than the one using a distribution x intensity product. A scoring index (SCORAD) combining extent, severity and subjective symptoms was mathematically derived from the first system and showed a normal distribution of the population studied. The final choice for the evaluation system was mostly made based on simplicity and easy routine use in outpatient clinics. Based on mathematical appreciation of weights of the items used in the assessment of AD, extent and subjective symptoms account for around 20% each of the total score, intensity items representing 60%. The so-designed composite index SCORAD needs to be further tested in clinical trials.
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              Cytokines and chemokines orchestrate atopic skin inflammation.

              Atopic dermatitis (AD) is a common pruritic and chronically relapsing inflammatory skin disease. The pathophysiology of AD includes disturbed skin barrier functions, frequent allergic responses against allergens, defects in the antimicrobial immune defense, and a genetic predisposition. In this review we summarize advances in our understanding of the complex interdependent network of members of the rapidly growing protein superfamilies of cytokines and chemokines that lead to the development of AD.
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                Author and article information

                Contributors
                jdejewska@yahoo.pl
                Journal
                Arch Dermatol Res
                Arch. Dermatol. Res
                Archives of Dermatological Research
                Springer-Verlag (Berlin/Heidelberg )
                0340-3696
                1432-069X
                12 September 2012
                12 September 2012
                December 2012
                : 304
                : 10
                : 795-801
                Affiliations
                [1 ]Department of Dermatology, Medical University of Warsaw, ul. Koszykowa 82A, 02-008 Warsaw, Poland
                [2 ]Department of Clinical Immunology, Medical University in Bialystok, ul. Waszyngtona 17, 17-274 Bialystok, Poland
                [3 ]Department of Microwave Safety, Military Institute of Hygiene and Epidemiology, ul. Szaserów 128, 04-141 Warsaw, Poland
                Article
                1290
                10.1007/s00403-012-1290-9
                3505524
                22968402
                6048e96d-c77e-4b52-9233-6ff1352cfb98
                © The Author(s) 2012
                History
                : 23 May 2012
                : 14 August 2012
                : 29 August 2012
                Categories
                Original Paper
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2012

                Dermatology
                atopic dermatitis,immunological markers,scorad index,t-regulatory cells
                Dermatology
                atopic dermatitis, immunological markers, scorad index, t-regulatory cells

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