Cerebellar Degeneration-related Antigen 1 Is Ubiquitously Expressed in Human Epidermis and Dermis.

Cerebellar degeneration-related antigen 1 (CDR1) was described to be expressed in the nervous system and in different types of cancer tissues. In the present study, we demonstrate that CDR1 is in addition ubiquitously expressed in human epidermis, dermis and isolated skin cells. Both CDR1 mRNA and protein were detected in human skin-derived mast cells, melanocytes, fibroblasts and keratinocytes, suggesting that CDR1 does not have a neuron-specific function.

The Differentiation-Associated Keratinocyte Protein Cornifelin Contributes to Cell-Cell Adhesion of Epidermal and Mucosal Keratinocytes.

Cornifelin (CNFN) has been identified as a protein component of epidermal corneocytes. Here, we investigated the tissue distribution of CNFN and potential consequences of CNFN deficiency on epithelial function in in vitro models of human skin and oral mucosa. Our detailed bioinformatics and immunostaining analysis revealed that CNFN is not only expressed in human epidermis but also in noncornifying oral mucosa.

The cytokine environment influence on human skin-derived T cells.

Skin resident T cells provide immediate immunologic responses at their specific location and play a role in the pathogenesis of skin diseases such as psoriasis. Recently, IL-9-producing T cells were described as a major T-cell subtype present in the skin, but knowledge on the biology and regulation of this T-cell subtype is scarce. Here, we investigated the cytokine influence on skin T cells with focus on IL-9-producing T cells because a better understanding of their biology may identify novel therapeutic approaches.

Different pro-angiogenic potential of γ-irradiated PBMC-derived secretome and its subfractions.

Secretomes from various cell sources exert strong regenerative activities on numerous organs, including the skin. Although secretomes consist of many diverse components, a growing body of evidence suggests that small extracellular vesicles (EVs) account for their regenerative capacity. We previously demonstrated that the secretome of γ-irradiated peripheral blood mononuclear cells (PBMCs) exhibits wound healing capacity.

Establishment of keratinocyte cell lines from human hair follicles.

The advent of organotypic skin models advanced the understanding of complex mechanisms of keratinocyte differentiation. However, these models are limited by both availability of primary keratinocytes and donor variability. Keratinocytes derived from cultured hair follicles and interfollicular epidermis were immortalized by ectopic expression of SV40 and hTERT.

A novel role for neutrophils in IgE-mediated allergy: Evidence for antigen presentation in late-phase reactions.

Background: Neutrophils and allergen-specific T cells accumulate in patients with allergic late-phase reactions (LPRs). Their presence is associated with severe inflammation. Cytokines, such as GM-CSF, IFN-γ, and IL-3, which are typically found in patients with allergic LPRs, have been proposed to convert neutrophils into antigen-presenting cells (APCs).

The Reticulum-Associated Protein RTN1A Specifically Identifies Human Dendritic Cells.

RTN1 is an endoplasmic reticulum-associated protein that was initially identified in neuronal tissues. Here we show that the main isoform RTN1A is a marker for dendritic cells. In the skin, HLA-DRCD1aCD207CD11c Langerhans cells were the only cells in the epidermis, and HLA-DRCD11c dendritic cells were the main cells in the dermis, expressing this protein.

The caspase-1 inhibitor CARD18 is specifically expressed during late differentiation of keratinocytes and its expression is lost in lichen planus.

Background: CARD18 contains a caspase recruitment domain (CARD) via which it binds to caspase-1 and thereby inhibits caspase-1-mediated activation of the pro-inflammatory cytokine interleukin (IL)-1β.

Objectives: To determine the expression profile and the role of CARD18 during differentiation of keratinocytes and to compare the expression of CARD18 in normal skin and in inflammatory skin diseases.

Methods: Human keratinocytes were induced to differentiate in monolayer and in 3D skin equivalent cultures.

Bioinformatics approach for choosing the correct reference genes when studying gene expression in human keratinocytes.

Reverse transcription polymerase chain reaction (qRT-PCR) has become a mainstay in many areas of skin research. To enable quantitative analysis, it is necessary to analyse expression of reference genes (RGs) for normalization of target gene expression. The selection of reliable RGs therefore has an important impact on the experimental outcome.

Fetal human keratinocytes produce large amounts of antimicrobial peptides: involvement of histone-methylation processes.

Antimicrobial peptides (AMPs), an important part of the innate immune system, are crucial for defense against invading microorganisms. Whereas AMPs have been extensively studied in adult skin, little is known about the impact of AMPs in the developing human skin. We therefore compared the expression and regulation of AMPs in fetal, neonatal, and adult keratinocytes (KCs) in vitro.

Histamine downregulates the Th1-associated chemokine IP-10 in monocytes and myeloid dendritic cells.

Background: Histamine is an important mediator of allergic diseases. It modulates the cytokine expression of various subtypes of antigen-presenting cells by four known receptors, H1R-H4R. The effects of histamine on myeloid dendritic cells (mDC) are unclear.

Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor.

Background: Epidermal hyperproliferation resulting in acanthosis is an important clinical observation in patients with atopic dermatitis, and its underlying mechanisms are not completely understood.

Objective: Because increased levels of histamine are present in lesional skin, we investigated the effect of histamine, especially with regard to histamine 4 receptor (H4R) activation, on the proliferation of human and murine keratinocytes.

Methods: The expression of H4R on human and murine keratinocytes was detected by using real-time PCR.

Secretome of peripheral blood mononuclear cells enhances wound healing.

Non-healing skin ulcers are often resistant to most common therapies. Treatment with growth factors has been demonstrated to improve closure of chronic wounds. Here we investigate whether lyophilized culture supernatant of freshly isolated peripheral blood mononuclear cells (PBMC) is able to enhance wound healing.

Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function.

Systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives, but demonstrate only modest anti-inflammatory activity. Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by the following mechanisms: (i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion.

Histamine down-regulates IL-27 production in antigen-presenting cells.

Histamine is a potent mediator in allergic inflammation with immunomodulatory properties. Since histamine was described to inhibit IL-12 production in human APCs, we hypothesized that also the expression of IL-27, a newly described member of the IL-12 family, which is present in inflammatory skin lesions, is modulated by histamine. Stimulation of human monocytes with histamine resulted in significant reduction of TLR ligand-induced IL-27 production in human monocytes.

Human memory Th17 cells express a functional histamine H4 receptor.

The histamine H4 receptor is functionally expressed on CD4(+) T cells and in particular on human CD4(+) Th2-polarized T cells. Interleukin (IL)-17-producing T cells (Th17 cells) represent a newly defined major CD4(+) T-cell subset, having been identified in psoriatic plaques and in acute skin lesions of atopic dermatitis where histamine is also present in high concentrations. To elucidate the role of the histamine H4 receptor (H4R) on these effector T cells, we polarized human memory T cells into Th17 cells.

Pathogenetic and therapeutic implications of the histamine H4 receptor in inflammatory skin diseases and pruritus.

Chronic inflammatory skin diseases such as atopic dermatitis (AD) are clinically characterized by erythematous and pruritic skin lesions, immunologically mediated by an inflammatory infiltrate consisting of T-cells, antigen presenting cells (APC) and eosinophilic granulocytes. Histamine levels are increased in lesions of inflammatory skin diseases. It is likely that histamine also plays a pathogenetic role since various relevant cell types such as T-cells and APC express functional histamine receptors.

The histamine H4 receptor is highly expressed on plasmacytoid dendritic cells in psoriasis and histamine regulates their cytokine production and migration.

Plasmacytoid dendritic cells (pDC) are present in inflammatory skin lesions, in particular, in psoriasis. In such lesions, the inflammatory mediator histamine is also detected in high amounts. We therefore investigated a possible interaction of pDC with histamine, especially via the most recently described histamine H(4) receptor (H(4)R).

The role of the histamine H4 receptor in atopic dermatitis.

The pathology of atopic dermatitis is orchestrated on the cellular level by several different cell types in the characteristic skin lesions. In such lesions, histamine as a mediator of many biological functions is also present in high concentrations. Most of the cells involved in the inflammatory responses express the histamine H1 and H2 receptors, but drugs targeting these receptors are not clinically effective.

Histamine H(4) receptor activation on human slan-dendritic cells down-regulates their pro-inflammatory capacity.

6-Sulpho LacNAc dendritic cells (slanDC) are a major population of human blood DC that are highly pro-inflammatory, as characterized by their outstanding capacity to produce tumour necrosis factor-α and interleukin-12 (IL-12) and to prime antigen-specific T-cell responses. SlanDC were found to be present in inflamed tissue such as atopic dermatitis, where high levels of histamine are also present. As histamine is an important regulator of allergic inflammation we investigated the role of histamine receptors, particularly the most recently identified histamine H(4) receptor (H(4) R), in modulating the pro-inflammatory function of slanDC.

The histamine H4 receptor is functionally expressed on T(H)2 cells.

Background: Histamine influences T-cell reactions via histamine receptors 1 and 2. The histamine receptor 4 (H(4)R) is the most recently identified histamine receptor and is also expressed on human CD4(+) T cells; however, its regulation and function are unclear.

Objective: To investigate expression, regulation, and function of the H(4)R on human CD4(+) T cells.

Histamine upregulates keratinocyte MMP-9 production via the histamine H1 receptor.

Skin inflammation and the migration of cells at the site of the immune response play an important role in allergic skin diseases. It has already been described that matrix metalloproteinase 9 (MMP-9) influences tissue remodeling and facilitates cell migration by proteolytic degradation of basal membrane components. The aim of this study was to investigate MMP-9 expression on human primary keratinocytes (KCs) upon stimulation with histamine, a potent mediator in allergic responses.