Expression of Co-stimulatory molecules on langerhans cells in lesional epidermis of human atopic dermatitis.
ABSTRACT Langerhans cells (LC) are immature dendritic cells (DC) present in the skin epithelium. To understand the molecular and cellular mechanisms governing the inflammatory reaction in atopic dermatitis (AD), the expression of the LC specific marker CD1a, a member of major histocompatibility (MHC)-like glycoproteins, and the co-stimulatory molecules CD80 and CD86, expressed on functionally mature dendritic cells, were counted in lesional biopsies and normal epidermis by an immunohistochemical method. CD1a specific staining was observed in both normal and AD lesion specimens. CD80 and CD86 positive cells with morphological characteristics of the LC were found in lesional AD epidermis, suggesting a high level of functional maturity of these cells and their involvement in chronic inflammatory disease.
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ABSTRACT: The present study was designed to investigate the effects of vasoactive intestinal peptide (VIP) on differentiation, maturation of dendritic cells (DCs) in vitro. DCs were derived from the murine bone marrow hemopoietic progenitor cells by culturing in RPMI 1640 complete medium supplemented with GM-CSF and IL-4 in the presence or absence of various concentrations of vasoactive intestinal peptide (VIP) and lipopolysaccharide (LPS). The phenotype of DCs was analyzed by flow cytometry. Mixed leukocyte reaction (MLR) was employed to measure the capacity of DC to stimulate the allogeneic T cells. IL-12p70 secretion by DC was examined by ELISA. In the absence of LPS, VIP, in a dose dependent manner, up-regulated the expression of CD80, CD86, CD54 and CD40, but down-regulated the expression of MHC class II molecule (Ia(b)). In the presence of LPS, VIP also dose dependently up-regulated the expression of CD80, CD86, CD54 and CD40, and down-regulated the expression of Ia(b). The capacity to stimulate alloreactive T cells and the production of IL-12p70 by DC were significantly augmented by VIP when compared with VIP-untreated DCs. These data suggest that VIP could promote the phenotypic and functional maturation of DCs, hereby regulating the type and outcome of the conducting immune response.International Immunopharmacology 07/2008; 8(10):1449-54. · 2.42 Impact Factor
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ABSTRACT: The innate immune pathway is important in the pathogenesis of asthma and eczema. However, only a few variants in these genes have been associated with either disease. We investigate the association between polymorphisms of genes in the innate immune pathway with childhood asthma and eczema. In addition, we compare individual associations with those discovered using a multivariate approach. Using a novel method, case control based association testing (C2BAT), 569 single nucleotide polymorphisms (SNPs) in 44 innate immune genes were tested for association with asthma and eczema in children from the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. The screening algorithm was used to identify the top SNPs associated with asthma and eczema. We next investigated the interaction of innate immune variants with asthma and eczema risk using Bayesian networks. After correction for multiple comparisons, 7 SNPs in 6 genes (CARD25, TGFB1, LY96, ACAA1, DEFB1, and IFNG) were associated with asthma (adjusted p-value<0.02), while 5 SNPs in 3 different genes (CD80, STAT4, and IRAKI) were significantly associated with eczema (adjusted p-value < 0.02). None of these SNPs were associated with both asthma and eczema. Bayesian network analysis identified 4 SNPs that were predictive of asthma and 10 SNPs that predicted eczema. Of the genes identified using Bayesian networks, only CD80 was associated with eczema in the single-SNP study. Using novel methodology that allows for screening and replication in the same population, we have identified associations of innate immune genes with asthma and eczema. Bayesian network analysis suggests that additional SNPs influence disease susceptibility via SNP interactions. Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants.Pediatric Allergy and Immunology 12/2011; 23(4):315-23. · 3.38 Impact Factor