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 responses however, especially in situations where a neoantigen is expressed, are likely to curtail expression and thereby limit the therapy. In vivo gene transfer to skin has been shown to induce transgene-specific immune responses. Ex vivo gene transfer approaches, where keratinocytes are transduced in culture and transplanted back to patient, however, may avoid signals provided to the immune system by in vivo administration of vectors. In the current study, we have developed a stable epidermal graft platform in immunocompetent mice to analyze host responses in ex vivo epidermal gene therapy. Using green fluorescent protein (GFP) as a neoantigen and an ex vivo retrovirus-mediated gene transfer to mouse primary epidermal cultures depleted of antigen-presenting cells (APCs), we show induction of GFP-specific immune responses leading to the clearance of transduced cells. Similar approach in immunocompetent mice tolerant to GFP resulted in permanent engraftment of transduced cells and continued GFP expression. Activation of transgene-specific immune responses in ex vivo gene transfer targeted to keratinocytes require cross-presentation of transgene product to APCs, a process that is most amenable to immune modulation. This model may be used to explore strategies to divert transgene-specific immune responses to less destructive or tolerogenic ones.
journal_name
Exp Dermatoljournal_title
Experimental dermatologyauthors
Lu Z,Ghazizadeh Sdoi
10.1111/j.1600-0625.2005.00351.xsubject
Has Abstractpub_date
2005-10-01 00:00:00pages
727-35issue
10eissn
0906-6705issn
1600-0625pii
EXD351journal_volume
14pub_type
杂志文章abstract::Irradiation of human keratinocytes with UVB (280-320 nm) in vitro and in vivo activates the metabolism of 7-dehydrocholesterol to hormonally active calcitriol. The production of calcitriol in the skin strongly depends on the photosynthesis of vitamin D(3) which is biologically inactive in the first instance. Vitamin D...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0625.2008.00810.x
更新日期:2009-02-01 00:00:00
abstract::Somatostatin (SST) is a regulatory peptide hormone that acts through five different G protein-coupled receptors (SSTR1-5). Whereas expression of all five SSTR subtypes in epidermis has been shown, the biological relevance of the SST/SSTR system in the skin is completely unknown. We show here that SST is expressed in h...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2010.01101.x
更新日期:2010-10-01 00:00:00
abstract::The outcome of a cutaneous immune response is critically dependent upon the ability of dendritic cells (DC) to migrate from skin to the draining lymph nodes - a process that is influenced by the cutaneous tissue microenvironment. Here, the role of fibroblasts - a major component of the dermal microenvironment - on the...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.12722
更新日期:2015-08-01 00:00:00
abstract::With rising skin cancer rates and interest in preventing photoaging, adjuvants for sunscreens are in high demand. The potential of curcumin has been posited due to its anti-inflammatory, antioxidant and wound healing properties. In prior studies, curcumin decreased UV-induced inflammation, apoptotic changes in human k...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.14282
更新日期:2021-01-15 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::We previously reported that sphingosine-1-phosphate (S1P) decreases melanin synthesis via extracellular signal-regulated protein kinase (ERK) activation and microphthalmia-associated transcription factor (MITF) degradation. Although FTY720 is an S1P structural analogue, the effects of FTY720 on melanogenesis are not c...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2010.01148.x
更新日期:2011-03-01 00:00:00
abstract::Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise one-third of all XP patients. Only four major reports compiled larger groups of XP-C patients from southern Europe (12 pts), North America (16 pts) and Africa (14 and 56 pts) as well as their genetic background (46 XPC mutations). We ide...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.12052
更新日期:2013-01-01 00:00:00
abstract::Calcium-mediated signals play important roles in epidermal barrier formation, skin homoeostasis and wound repair. Calmodulin 4 (Calm4) is a small, Ca2+ -binding protein with strong expression in suprabasal keratinocytes. In mice, Calm4 first appears in the skin at the time of barrier formation, and its expression incr...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/exd.12568
更新日期:2015-01-01 00:00:00
abstract::Proteases and their receptors have poorly understood roles in skin fibrosis and systemic scleroderma (SSc). We examined the role of protease-activated receptors (PAR(1) and PAR(2) ) in the pathophysiology of human SSc and skin fibrosis. Immunohistochemistry showed that PAR(1) immunoreactivity was positive in fibroblas...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/j.1600-0625.2010.01184.x
更新日期:2011-01-01 00:00:00
abstract::The best characterized signalling pathway employed by transforming growth factor-beta (TGF-β) is the Smad pathway. We focused on Smad4, because it is essential for the activation of Smad-dependent target genes. We aimed to explore the possibility of inhibiting scar formation after wounding by blocking TGF-β signalling...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2010.01186.x
更新日期:2011-02-01 00:00:00
abstract::Chronic exposure to ultraviolet (UV) radiation alters components of the skin. We previously reported that chronic low-dose UV irradiation induced wrinkle formation but did not significantly alter dermal components of hairless mice. In the present study, we examined whether the epidermal changes by UV irradiation could...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1034/j.1600-0625.12.s2.4.x
更新日期:2003-01-01 00:00:00
abstract::The correlation between the degrees of integrity and cohesion in healthy human Stratum corneum (SC) and the properties of the SC lipid matrix could be examined non-invasively in vivo using ATR-FTIR spectroscopy and measurements of pH, conductance, and transepidermal water loss (TEWL) taken in the course of tape-stripp...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2010.01164.x
更新日期:2011-03-01 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::Wool fibres are hairs and the term 'wool' is usually restricted to describe the fine curly hairs that constitute the fleece produced by sheep. In a broader sense, it can be used to describe the fleeces produced by related species such as goat or yak. Research into the biology of wool growth and the structure of the wo...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0625.2006.00512.x
更新日期:2006-12-01 00:00:00
abstract::A number of single gene mutations in laboratory mice produce hair follicle defects resulting in deformed hair shafts. The radiation-induced (SB/LeJ-Foxq1(sa)) satin mutant mice have a satin-like sheen to their hair and dilute colouration. This sheen is due to failure of the hair shafts to develop normal medullas, whil...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/exd.12106
更新日期:2013-03-01 00:00:00
abstract::White adipose tissue is known to be involved in numerous physiological processes such as insulin-mediated functions, lipid and glucose metabolism, vascular changes and coagulation. These processes are mainly mediated by adipokines that are secreted either from adipocytes or cells of the stromal-vascular fraction of ad...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2011.01402.x
更新日期:2012-01-01 00:00:00
abstract::Rosacea is one of the most common dermatoses of adults. Although the detailed pathophysiology remains unknown, it is thought that rosacea is caused by a consistently aberrant, innate immune response, and that LL-37 plays an important role. However, involvement of the inflammatory cytokine IL-33 has not yet been studie...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.13702
更新日期:2018-09-01 00:00:00
abstract::Malignant melanoma is a tumor characterized by the uncontrolled proliferation of melanocytes, mainly in skin, but also in eyes. Its incidence is rising each year. To improve the diagnosis and treatment of the tumor, it is essential to develop new effective methods to early detect and characterize melanoma. Previously,...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2012.01461.x
更新日期:2012-05-01 00:00:00
abstract::Neutrophil extravasation is central to inflammatory skin diseases like psoriasis and atopic dermatitis. In vivo, neutrophils have been shown to migrate through cell-to-cell junctions (paracellular pathway) or directly through the body of the endothelial cell (transcellular pathway). In vitro, however, neutrophil migra...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/j.1600-0625.2008.00796.x
更新日期:2009-01-01 00:00:00
abstract::Recently, 3% diclofenacnatrium gel (diclofenac) was introduced for the treatment of actinic keratoses. Data on photocarcinogenesis of topical diclofenac are limited, and we wished to investigate whether topical diclofenac can accelerate photocarcinogenesis using simulated solar radiation (SSR). Diclofenac was applied ...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2010.01215.x
更新日期:2011-04-01 00:00:00
abstract::Opioids exert major effects not only in the central nervous system but also in immune responses. We investigated the effects of μ-opioid peptides, secreted by tumor cells, on anti-tumor immune responses. For this purpose, tumor growth was studied in wild-type and μ-opioid receptor-deficient (MOR-/-) mice injected with...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2010.01158.x
更新日期:2011-01-01 00:00:00
abstract::Mast cells (MCs) have been intensely investigated over the past two decades, e.g. the numbers of PubMed-listed reports on MCs have steadily increased and doubled over the past twenty years. Surprisingly, many recent findings that have fundamentally changed our understanding of MC biology and functions have yet to be s...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0625.2005.00369.x
更新日期:2005-12-01 00:00:00
abstract::CD44 is a family of cell-surface receptors on human lymphocytes that act as co-stimulatory molecules leading to the induction of effector functions in T cells. We have analyzed primary cutaneous malignant melanomas with clinical and histologic signs of tumor regression using immunohistochemistry and observed the predo...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1034/j.1600-0625.2003.00044.x
更新日期:2003-04-01 00:00:00
abstract::Activating transcription factor 3 (ATF3) expression is increased in erythema multiforme and is regulated by IFN-gamma in human keratinocytes. Experimental Dermatology 2010; 19: e310-e313. Abstract: Activating transcription factor 3 (ATF3) is a member of the ATF/cyclic AMP responsive element-binding protein (CREB) fami...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/j.1600-0625.2009.01008.x
更新日期:2010-08-01 00:00:00
abstract::The reliability of the methods currently used for diagnosing hair loss is ill defined. We studied 41 subjects complaining of hair loss, including androgenetic alopecia and telogen effluvium, and compared the results obtained with the modified wash test (MWT) and TrichoScan(®) . Data were analysed statistically with th...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/exd.12164
更新日期:2013-07-01 00:00:00
abstract::Shprintzen-Goldberg syndrome (SGS) is a rare disorder characterized by a Marfan-like habitus, mental retardation and craniosynostosis. Cardiac abnormalities, such as aortic root dilation have also been noted as well as several skeletal abnormalities. Its nosological status is unclear as it is hard to delineate SGS fro...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2007.00648.x
更新日期:2008-04-01 00:00:00
abstract::Ultraviolet B (UVB) radiation induces inflammation in the skin specifically at the site of exposure. We unexpectedly found that UVB-induced inflammation was not induced in gp91phox-depleted mice. To test whether gp91phox is directly involved in UVB-induced inflammation, neutrophil- and hyaluronic acid-depleted mice we...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.12032
更新日期:2012-12-01 00:00:00
abstract::Dendritic cells (DC) are key elements of the immune system. In peripheral tissues, they function as sentinels taking up and processing antigens. After migration to the draining lymph nodes, the DC either present antigenic peptides by themselves or transfer them to lymph node-resident DC. The skin is the primary interf...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2010.01116.x
更新日期:2010-08-01 00:00:00
abstract::Patch-clamp recordings were carried out in the inside-out configuration in human keratinocytes of the cell line HaCaT. Patch pipettes were filled with 150 mM KCl, 1 mM CaCl(2) and 10 mM HEPES. In symmetrical KCl solutions, single channel currents from a large conductance channel (about 170 pS) were measured. Replaceme...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1034/j.1600-0625.2002.110405.x
更新日期:2002-08-01 00:00:00
abstract::Allergen-induced emigration and maturation of dendritic cells (DC) are pivotal steps in sparking off allergic contact dermatitis. In vitro models, reflecting these steps, may provide tools for assessment of sensitizing capacities of putative contact allergens. Here, we evaluated the applicability of such models for a ...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1034/j.1600-0625.2003.00077.x
更新日期:2003-10-01 00:00:00