Epidermal Langerhans cells (LCs) show extraordinary immunostimulatory capacity and play a key role in the initiation and regulation of immune responses. Studies of LC biology are currently the focus of efforts to engineer immune responses and to better understand the immunopathology of cutaneous diseases. Here we identified and characterized a population of LC precursors that were resident in human skin. These immediate precursors expressed CD14, langerin and functional CCR6. When cultured with transforming growth factor-beta1 alone, they had the potential to differentiate into epidermal LCs; when cultured in the presence of granulocyte macrophage-colony-stimulating factor and interleukin 4 they differentiated into functionally mature dendritic cells. Identification and characterization of these LC precursors provided insight into LC biology and the mechanism(s) through which LCs repopulate the epidermis.
Acquired ichthyosis (AI) is a nonhereditary cutaneous disorder characterized by dry, rough skin with prominent scaling that involves significant portions of the body. It has been associated with malignancies; autoimmune/inflammatory, metabolic, endocrine, and infectious diseases; and medication use. Most microscopic studies of AI exhibit hyperkeratosis with a reduced or absent granular layer. Because AI has been linked to a variety of conditions, the workup of a patient presenting with this finding can be complex. We present an update on AI to provide clinicians with direction regarding the assessment and treatment of patients presenting with AI. An algorithm for the evaluation of patients presenting with AI is provided.
Gene therapy techniques can be important tools for the induction and control of immune responses. Antigen delivery is a critical challenge in vaccine design, and DNA-based immunization offers an attractive method to deliver encoded transgenic protein antigens. In the present study, we used a gene gun to transfect human skin organ cultures with a particular goal of expressing transgenic antigens in resident cutaneous dendritic cells. Our studies demonstrate that when delivered to human skin, gold particles are observed primarily in the epidermis, even when high helium delivery pressures are used. We demonstrate that Langerhans cells resident in the basal epidermis can be transfected, and that
Mutant Chinese hamster ovary cells altered in glycoproteins have been isolated by selecting for ability to survive exposure to [6-3H]fucose. Mutagenized wildtype cells were permitted to incorporate [3H]fucose to approximately 1 cpm of trichloroacetic acid-insoluble radioactivity per cell and then frozen for several days to accumulate radiation damage. The overall viability of the population was reduced by 5-to 50-fold. Four consecutive selection cycles were carried out. The surviving cells were screened by replica plating-fluorography for clones showing decreased incorporation of fucose into trichloroacetic acid-insoluble macromolecules. Considerable enrichment for cells deficient in fucose uptake or incorporation into proteins (or both) was found in populations surviving the later selection cycles. Two mutant clones isolated after the fourth selection cycle had the same doubling time as the wild type, but contained only 30 to 40% as much fucose bound to proteins as the wild type. Sialic acid contents of the mutants and the wild type were similar. The mutants differed quantitatively and qualitatively from the wild type and from each other with respect to total glycoprotein profiles as visualized by sodium dodecyl sulfate gel electrophoresis. Differences were also found in resistances to cytotoxicity of lectins such as concanavalin A and wheat germ agglutinin.Glycoprotein components of mammalian cell surfaces are thought to play vital roles in such processes as regulation of cell growth, intercellular recognition, and cellular adhesion (8,31,32). A powerful approach for investigating relationships between glycoprotein structure and functions and for elucidating the biosynthesis of the oligosaccharide moieties of these molecules is to examine the phenotypes of somatic cell mutants with altered glycoprotein synthesis (5,10,14,16,18,20,22). One notably successful tactic for the isolation of such glycoprotein mutants has been the selection of cells resistant to cytotoxic lectins (4, 6, 9, 11, 23-25, 30, 33). Such resistance presumably reflects alterations in cell surface glycoproteins, particularly those which are part of or adjacent to the lectin receptors. Recent studies have suggested that more than one sugar may be involved in the surface recognition system for some lectins (2).We have initiated studies based on an alternative method for selection of glycoprotein mutants with altered oligosaccharide moieties. Our
In our department, Class I topical steroids are commonly used in the treatment of psoriasis. The superpotent topicals are often used as an adjunct to systemic therapy and will likely remain a mainstay of psoriasis therapy.
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