Abstract:
:Optimized delivery of antigens combined with sustainable maturation of dendritic cells (DCs) is crucial for generation of effective antitumoral immune responses. Multiple approaches for ex vivo antigen loading and improvement in immunogenicity have been described. We have recently established a single-step protocol consisting of a fusion peptide (a sequence of the melanoma antigen Melan-A and a cationic cell-penetrating HIV TAT domain) bound in complexes with a toll-like receptor agonist. As the exact cellular uptake mechanisms of TAT-coupled antigens have been a matter of considerable debate and significantly depend on cell type, cargo and concentrations, we evaluated internalization routes into human immature DCs in comparison with non-phagocytic cell lines. We found that Melan-A-TAT fusion peptide uptake by DCs is mainly energy dependent, superior compared with polylysine-coupled Melan-A and significantly higher in DCs as compared with Jurkat cells or HUVECs. Furthermore, we could track the uptake of the fusion peptide exclusively through early endosomes to lysosome compartments after 90 min by fluorescence microscopy and immunoelectron microscopy. Specific endocytosis inhibitors revealed major internalization of the fusion peptide by DCs via clathrin-mediated endocytosis, whereas uptake by non-phagocytic HUVECs differed significantly, involving macropinocytosis as well as clathrin-mediated endocytosis. As our understanding of the processes involved in internalization of TAT-coupled cargos by human DCs broadens, and DC activation becomes available by single-step procedures as described, further development of simultaneous DC maturation and intra-cellular peptide targeting is warranted.
journal_name
Exp Dermatoljournal_title
Experimental dermatologyauthors
Buhl T,Braun A,Forkel S,Möbius W,van Werven L,Jahn O,Rezaei-Ghaleh N,Zweckstetter M,Mempel M,Schön MP,Haenssle HAdoi
10.1111/exd.12285subject
Has Abstractpub_date
2014-01-01 00:00:00pages
20-6issue
1eissn
0906-6705issn
1600-0625journal_volume
23pub_type
杂志文章abstract::Dermal white adipose tissue (DWAT) is a main component of human skin, composed of individual lipid-laden mesenchymal cells known as dermal adipocytes (DAs). Besides their well-known role in lipid storage and release, DAs also promote skin immunity, wound healing and hair follicle cycling and are important players in c...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/exd.13549
更新日期:2018-06-01 00:00:00
abstract::The bioactive lysophospholipid sphingosine-1-phosphate (S1P) is best known for its activity as T-cell-active chemoattractant regulating the egress of T cells from the lymph node and, consequently, the availability of T cells for migration into peripheral tissues. This physiological role of S1P is exploited by the drug...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/exd.13174
更新日期:2017-03-01 00:00:00
abstract::The proliferative responses of cells to mitogens decrease during aging, and this may result from age-related defects in signal transduction in response to mitogens. In this study, we have investigated the age-related alteration of responses to epidermal growth factor (EGF) in cultured human keratinocytes that were sen...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.0906-6705.2005.00317.x
更新日期:2005-07-01 00:00:00
abstract::We have previously reported that lymph node cells generated chemotactic factors for Langerhans cells (LCs) in the induction phase of contact dermatitis. In order to clarify the chemotactic factors involved in migration to the regional lymph nodes, we investigated the migratory activity of murine LCs toward several cyt...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.1998.tb00300.x
更新日期:1998-02-01 00:00:00
abstract::Dermal papilla cells (DPC) control the growth character of the hair follicle through their elaboration of mitogenic factors and extracellular matrix components. Further, the dermal papilla is a primary site of androgen action in the hair follicle. Interleukin-1alpha (IL-1alpha) is prominent in skin wounding and inflam...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2006.00462.x
更新日期:2006-10-01 00:00:00
abstract::Vitiligo is a chronic skin disease characterized by the appearance of zones of depigmentation. It is mostly described as an autoimmune disease in which the immune system destroys the melanocytes. Consistent with this origin, genetic studies have implicated genes encoding proteins mediating the immune response targetin...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/exd.13858
更新日期:2019-06-01 00:00:00
abstract::In systemic scleroderma (SSc) excessive deposition of collagen leads to fibrosis of various tissues including the skin. Previous studies have demonstrated that scleroderma fibroblasts in explant monolayer cultures are heterogeneous with respect to their levels of collagen synthesis. The critical role played by the ext...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.1992.tb00187.x
更新日期:1992-11-01 00:00:00
abstract::The role of placebo and nocebo effects-that is positive or negative treatment effects that are entirely a consequence of the patient's expectations and beliefs about a treatment outcome in terms of efficacy, safety, usability or side effects-has been shown for almost all types of diseases and physiological response sy...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.13158
更新日期:2017-01-01 00:00:00
abstract::The last decade has seen a considerable improvement in the understanding of the biology of melanoma. Advances have come in the understanding of the importance of critical oncogenes and tumour suppressor genes, epigenetic phenomena, signalling pathways, drug resistance mechanisms, the pivotal role of the local immune s...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0625.2007.00673.x
更新日期:2008-05-01 00:00:00
abstract::Recent studies have demonstrated that keratinocytes closely participate in sensory transduction, and therefore, intra-epidermal free nerve endings are not exclusive transducers of pain. This discovery implies the existence of close afferent communication from keratinocytes to sensory neurons. Although reciprocal inter...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/exd.13411
更新日期:2018-01-01 00:00:00
abstract::Psoriasis is an inflammatory skin disease often associated with obesity. The anti-inflammatory adipokine vaspin, a suggested serine proteinase inhibitor of the serpin family, is discussed as a new link between inflammation and obesity. Here, we demonstrate that - different from healthy controls - vaspin serum levels i...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/j.1600-0625.2012.01460.x
更新日期:2012-04-01 00:00:00
abstract::Patients with the blistering disease, epidermolysis bullosa (EB), frequently suffer from chronic wounds that become colonized by pathogenic bacteria, such as Staphylococcus aureus. To determine S. aureus colonization rates in patients with EB, swabs were collected from the anterior nares, throats and wounds of 52 Dutc...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/j.1600-0625.2012.01502.x
更新日期:2012-06-01 00:00:00
abstract::Type-1 cytokine-producing T cells are important in the pathogenesis of psoriasis vulgaris, for which efficient therapy is provided by means of narrow-band ultraviolet-B (NB-UVB). The expression of the type-1 cytokine interferon-gamma (IFN-gamma) is regulated by interleukin-12 (IL-12), IL-15, IL-18 and IL-23; however, ...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.0906-6705.2004.00246.x
更新日期:2004-12-01 00:00:00
abstract::Flavonoids belong to a large group of polyphenolic compounds that are widely present in plants. Certain flavonoids, including naringenin, have cytoprotective properties. Although the antioxidant effect has long been thought to be a crucial factor accounting for the cellular effects of flavonoids, mitochondrial channel...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.13903
更新日期:2019-05-01 00:00:00
abstract::Bullous pemphigoid (BP) and pemphigoid gestationis (PG) are acquired autoimmune subepidermal blistering diseases characterized by autoantibodies against the hemidesmosomal proteins BP180/type XVII collagen and BP230. In the vast majority of BP and PG patients, these autoantibodies bind to epitopes clustered within the...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2007.00592.x
更新日期:2007-09-01 00:00:00
abstract::Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra- and extracellular modifications are needed to make functional collagen molecules, intracellular pos...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/exd.14197
更新日期:2021-01-01 00:00:00
abstract::Volatile organic compounds emitted by human skin were sampled before and after acute barrier disruption of the volar forearm to investigate the significance of this approach to skin physiology research. A small wearable housing integrating a solid-phase micro-extraction fibre permitting rapid enclosed headspace sampli...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.13344
更新日期:2017-10-01 00:00:00
abstract::While the central role of mast cells (MC) in allergy and inflammation is well-appreciated, much less is known about their physiological functions. The impressive battery of potent growth modulatory MC products, and increasing evidence of MC involvement in hyperproliferative and fibrotic disorders suggest that tissue r...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0625.1995.tb00256.x
更新日期:1995-08-01 00:00:00
abstract::Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease combining inflammatory, vasculopathic and fibrotic manifestations. Skin features, which give their name to the disease and are considered as diagnostic as well as prognostic markers, have not been thoroughly investigated in terms of therapeutic...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/exd.13806
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Recently, germline variants of the melanocortin-1 receptor (MC1R) have been shown to be associated with an increased risk for BRAF mutant but not BRAF wild-type cutaneous melanoma. Similar to melanoma, BRAF mutations are also commonly found in papillary thyroid carcinomas. Furthermore, patients with melanoma...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2008.00827.x
更新日期:2009-06-01 00:00:00
abstract::Chromatin-IgG complexes appear as electron dense structures (EDS) in glomerular basement membranes in lupus nephritis. Here, we present results of comparative analyses of the composition of EDS in murine lupus dermatitis and nephritis. One focus was to perform an analytical approach to understand why such complex stru...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2010.01064.x
更新日期:2010-08-01 00:00:00
abstract::Epidermal gene therapy may benefit a variety of inherited skin disorders and certain systemic diseases. Both in vivo and ex vivo approaches of gene transfer have been used to target human epidermal stem cells and achieve long-term transgene expression in immunodeficient mouse/human chimera models. Immunological respon...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2005.00351.x
更新日期:2005-10-01 00:00:00
abstract::Sunburn cell (SBC) formation in the epidermis is a characteristic consequence of ultraviolet radiation (UVR) exposure at doses around or above the minimum erythema dose. SBC have been identified morphologically and biologically as keratinocytes undergoing apoptosis. There is evidence that SBC formation is a protective...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1034/j.1600-0625.2001.010003155.x
更新日期:2001-06-01 00:00:00
abstract::Antibodies, specific to murine DEC205, can be used to target antigens to dendritic cells. The immunodominant domain of human type XVII collagen, hNC16A, was fused to this antibody (DEC-hNC16A) and was administered as expression plasmid by gene gun transfection with the aim of inducing tolerance to human type XVII coll...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/j.1600-0625.2012.01474.x
更新日期:2012-05-01 00:00:00
abstract::Murine model systems are critically required tools for the investigation of unknown mechanisms of melanoma development and metastasis and for developing more efficient therapies. The Tg(Grm1)EPv melanoma mouse model is characterized by spontaneous development of pigmented cutaneous melanomas at hairless skin regions, ...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/j.1600-0625.2012.01560.x
更新日期:2012-10-01 00:00:00
abstract::Ultraviolet (UV) triggers induction of matrix metalloproteinase-1 (MMP-1) and also induces the rapid appearance of p53 protein in the epidermis and dermal fibroblasts. However, little is known about the role of p53 on MMP-1 expression in human skin. Here, we investigated the effects of p53 on basal and UV-induced MMP-...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2008.00729.x
更新日期:2008-11-01 00:00:00
abstract::Mast cells, eosinophils and basophils are central effector immune cells in allergic skin inflammation including atopic dermatitis (AD). Recent studies revealed that the bidirectional interaction between these three immune cell types (mast cells, eosinophils and basophils) and the nervous system is involved in the path...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/exd.14014
更新日期:2019-12-01 00:00:00
abstract::For decades, an extensive debate is continued on the pathophysiology of vitiligo. Numerous hypotheses have been put forward, and many supported by well-documented arguments. Regardless of the initiating steps, most experts agree that an immune-based melanocyte destruction is responsible for the final steps leading to ...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.13069
更新日期:2017-07-01 00:00:00
abstract::In this study, we investigated the process of X-ray-induced apoptosis of skin keratinocyte, and the functional role of protein kinase C delta (PKCdelta) and downstream signalling cascade. High-dose X-ray irradiation (10 Gy) led to the apoptosis of HaCaT keratinocyte, accompanied by PKCdelta cleavage. Treatment with PK...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2008.00761.x
更新日期:2009-01-01 00:00:00
abstract::Several association studies and GWAS on melanoma skin cancer risk have reported statistically significant signals on 9p21.3 region, where MTAP gene maps. None of the associated SNPs identified in these studies lie in the coding region of the gene and the causative relation of risk alleles with melanoma predisposition ...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/exd.13247
更新日期:2017-08-01 00:00:00