Distribution of ATPase-positive Langerhans cells in normal adult human skin

Chen, H.; Yuan, Jingtao; Wang, Y.; Silvers, Willys K.

doi:10.1111/j.1365-2133.1985.tb02406.x

Cited by 57 publications

(24 citation statements)

References 11 publications

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“…However, LC density was considerably lower in their control subjects than in ours. We have no explanation for this discrepancy, but the LC number established in our control subjects corresponds to the findings of several previous studies (6,22). …”

Section: Diabetesdiabetesjournalsorg Strom and Associates 1151supporting

confidence: 82%

Pronounced Reduction of Cutaneous Langerhans Cell Density in Recently Diagnosed Type 2 Diabetes

et al. 2014

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Immune-mediated processes have been implicated in the pathogenesis of diabetic polyneuropathy. Langerhans cells (LCs) are the sole dendritic cell type located in the healthy epidermis and exert tolerogenic immune functions. We aimed to determine whether alterations in cutaneous LC density and intraepidermal nerve fiber density (IENFD) are present in patients with recently diagnosed type 2 diabetes. Skin biopsy specimens from the distal leg from 96 type 2 diabetic patients and 75 healthy control subjects were used for quantification of LC density and IENFD. LCs and IENFs were labeled using immunohistochemistry. Nerve conduction studies, quantitative sensory testing, and neurological examination were used to assess peripheral nerve function. LC density was markedly reduced in the diabetic group compared with the control group, but did not correlate with reduced IENFD or peripheral nerve function. Multivariate linear regression analysis revealed a strong association between LC density and whole-body insulin sensitivity in women but not in men with diabetes. Prospective studies should establish whether the pronounced reduction of cutaneous LCs detected in recently diagnosed type 2 diabetes could promote a cutaneous immunogenic imbalance toward inflammation predisposing to polyneuropathy and foot ulcers. Recent evidence suggests the involvement of inflammatory processes in the pathogenesis of type 2 diabetes (T2D) (1) and its complications such as polyneuropathy (2). Diabetic neuropathy is associated with extensive morbidity, increased mortality, and reduced quality of life (3). A distal leg skin biopsy specimen with quantification of intraepidermal nerve fiber density (IENFD) is a reliable and efficient technique to assess the diagnosis of small fiber neuropathy (SFN) (4). However, the pathophysiological processes triggering the loss of IENFs in diabetic neuropathy are unknown. Langerhans cells (LCs) are the sole dendritic cells located in the healthy epidermis. IENFs have been shown to have an immune-modulatory effect on LCs (5). This finding indicates a close relationship between the nervous system and the function of distinct immune system components. In patients with type 1 diabetes, cutaneous LC density was markedly reduced immediately at diabetes RESEARCH DESIGN AND METHODS SubjectsThe study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of the Heinrich Heine University, Düsseldorf. All participants provided a written informed consent. Healthy control subjects (n = 75) and patients with recently diagnosed T2D (n = 96) were studied. Subjects with T2D were participants of the prospective German Diabetes Study (GDS), which evaluates the long-term course of diabetes and its sequelae (9). Inclusion criteria for entry into the GDS were type 1 or type 2 diabetes, known diabetes duration #1 year, and 18-69 years of age. Exclusion criteria were secondary diabetes, pregnancy, severe diseases (cancer), psychiatric disorders, immunosuppressive therapy, limited cooper...

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Section: Diabetesdiabetesjournalsorg Strom and Associates 1151supporting

confidence: 82%

Pronounced Reduction of Cutaneous Langerhans Cell Density in Recently Diagnosed Type 2 Diabetes

et al. 2014

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“…LCs are believed to play an important role in the immune responses to EPI. LCs, which account for 2 to 4% of all epithelial cells in the viable epidermis, are known potent APCs (2,5,11,14,53 (8,11,30). In the present study, EPI delivered antigens to a skin target area of approximately 113 mm 2 , which comprises approximately 10 5 LCs.…”

Section: Discussionmentioning

confidence: 99%

Epidermal Powder Immunization Induces both Cytotoxic T-Lymphocyte and Antibody Responses to Protein Antigens of Influenza and Hepatitis B Viruses

Chen

Weis

Chu

et al. 2001

J Virol

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Cytotoxic T lymphocytes (CTL) play a vital role in host defense against viral and intracellular bacterial infections. However, nonreplicating vaccines administered by intramuscular injection using a syringe and needle elicit predominantly humoral responses and not CTL responses. Here we report that epidermal powder immunization (EPI), a technology that delivers antigens on 1.5-to 2.5-m gold particles to the epidermis using a needle-free powder delivery system, elicits CTL responses to nonreplicating antigens. Following EPI, a majority of the antigen-coated gold particles were found in the viable epidermis in the histological sections of the target skin. Further studies using transmission electron microscopy revealed the intracellular localization of the gold particles. Many Langerhans cells (LCs) at the vaccination site contained antigen-coated particles, as revealed by two-color immunofluorescence microscopy, and these cells were found in the draining lymph nodes 20 h later. Immune responses to several viral protein antigens after EPI were studied in mice.

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“…The EC sensitization method, which utilises a delayed-type contact hypersensitivity sensitization, was suitable for the sensitization phase. Guinea pig skin and human skin have similar percutaneous permeability (Barbero and Frasch, 2009) and numbers of Langerhans cells (Chen et al, 1985;Wolff and Winkelmann, 1967). As such, a combination of PCA and EC sensitization in guinea pig models is potentially useful.…”

Section: Introductionmentioning

confidence: 99%

Anaphylactic augmentation by epicutaneous sensitization to acid-hydrolyzed wheat protein in a guinea pig model

et al. 2015

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-Recent reports suggest that hydrolyzed wheat protein (HWP) variants such as Glupearl® 19S (GP19S) induce immediate-type hypersensitivity via epicutaneous (EC) sensitization. The identification of strong allergens is a key step in product assessment before commercial launch. However, few reports have described the estimation of actual and potential anaphylactic sensitizing capacity. In this study we assessed the strength of both the actual and potential anaphylactic sensitizing capacity by investigating the immediate-type hypersensitivity inducing potential of HWP compared with gluten. We assessed these strengths via the EC route using an EC or intradermal (ID) sensitization method. We quantified the strength of immediate-type hypersensitivity by evaluating the titer of serum antibodies isolated from sensitized subjects using passive cutaneous anaphylaxis (PCA) reactions. We also evaluated the cross-reactivity between GP19S and gluten. GP19S and gluten applied by both the sensitization methods induced obvious IgG1-mediated PCA reactions. GP19S had stronger sensitizing potential than gluten, according to the serum titers and dye spot diameters. The difference in antibody titers between GP19S and gluten was 16-fold for the EC method versus 2-fold for the ID method. GP19S cross-reacted with gluten. Acid hydrolysis of gluten increased anaphylactic sensitizing capacity in the EC method. To our knowledge, our study is the first to quantitatively confirm that HWP and gluten can induce immediate-type hypersensitivity through an intact skin. These findings suggest that acid-HWP imposes a higher risk of EC sensitization than gluten because of the ease with which the former confers a sensitizing effect through the intact skin.

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Distribution of ATPase-positive Langerhans cells in normal adult human skin

Cited by 57 publications

References 11 publications

Pronounced Reduction of Cutaneous Langerhans Cell Density in Recently Diagnosed Type 2 Diabetes

Pronounced Reduction of Cutaneous Langerhans Cell Density in Recently Diagnosed Type 2 Diabetes

Epidermal Powder Immunization Induces both Cytotoxic T-Lymphocyte and Antibody Responses to Protein Antigens of Influenza and Hepatitis B Viruses

Anaphylactic augmentation by epicutaneous sensitization to acid-hydrolyzed wheat protein in a guinea pig model

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