Langerhans cell hyperplasia and IgE expression in canine atopic dermatitis

Langerhans cells appear to be critical for IgE-mediated allergen capture and presentation in human atopic dermatitis. The present study sought to determine whether epidermal (i.e Langerhans cells) and dermal dendritic cells in the skin of dogs with atopic dermatitis are hyperplastic and expressed surface IgE. Frozen sections of lesional or nonlesional atopic and normal control canine skin were immunostained with CD1a-, CD1c-, and IgE-specific monoclonal antibodies. The enumeration of cells was performed by morphometry in both the epidermis and the dermis. Cell counts were compared with each individual’s total serum IgE levels. Higher numbers of epidermal and dermal dendritic cells were present in atopic dogs than in normal control animals. Epidermal Langerhans cell counts were significantly higher in lesional than in nonlesional atopic specimens. IgE⁺ dendritic cells were observed in lesional atopic epidermis and dermis, and nonlesional atopic dermis, but not in normal control skin specimens. The percentages of IgE⁺ dendritic cells were correlated with each patient’s total serum IgE levels. These results demonstrate dendritic cell hyperplasia and IgE expression in canine atopic dermatitis. Increased epidermal Langerhans cell counts in lesional specimens suggest an epidermal allergen contact in canine atopic dermatitis.     

A reducing microenvironment leads to the generation of FcepsilonRIhigh inflammatory dendritic epidermal cells (IDEC)

Inflammatory dendritic epidermal cells present in skin lesions of the atopic eczema/dermatitis syndrome display the highest expression of the high-affinity receptor for IgE (FcepsilonRI), ever detected on human antigen-presenting cells. Owing to the instability of the FcepsilonRI (alphagammagamma) complex and fast cleavage from the cell surface during the interleukin-4/granulocyte-macrophage colony-stimulating factor driven in vitro differentiation of monocytes, a method to generate inflammatory dendritic epidermal cells was not at our disposal in the past and the amount of ex vivo isolated inflammatory dendritic epidermal cells available for functional assays was limited. Therefore, information about the role of inflammatory dendritic epidermal cells and FcepsilonRI on this dendritic cell subtype in atopic and inflammatory skin diseases is completely missing. In this study, we were able to: (i) increase the expression of a functional FcepsilonRI complex on the cell surface of immature monocyte-derived dendritic cells from atopic donors by creating a reducing microenvironment; (ii) enhance significantly the intracellular pool of the FcepsilonRIgamma chains, which is the limiting parameter for the FcepsilonRI surface expression; and (iii) generate monocyte-derived dendritic cells displaying the phenotypical characteristics of inflammatory dendritic epidermal cells, producing high amounts of proinflammatory cytokines and chemokines similar to the cytokines found in lesional skin of the atopic eczema/dermatitis syndrome. Altogether the high expression of functional FcepsilonRI on these cells enables us for the first time to study inflammatory dendritic epidermal cells and FcepsilonRI-mediated mechanisms of inflammatory dendritic epidermal cells in vitro, in order to shed light on the putative role of this important cell type in the atopic eczema/dermatitis syndrome.     

Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases

Epidermal dendritic cells found in inflamed skin include Langerhans cells and the recently identified population of inflammatory dendritic epidermal cells. Another subset of dendritic cells in humans is the plasmacytoid dendritic cell in peripheral blood, which is characterized by the production of large amounts of type I interferon (interferon-alpha and interferon-beta) upon viral infection. We hypothesized that plasmacytoid dendritic cells might be involved in anti-viral defense mechanisms of the skin. Here we investigated plasmacytoid dendritic cells, inflammatory dendritic epidermal cells, and Langerhans cells in epidermal single cell suspensions of normal looking skin from healthy volunteers and of lesional skin from patients with different inflammatory skin diseases. Langerhans cells were found in normal and in inflamed skin samples. In normal skin, plasmacytoid dendritic cells and inflammatory dendritic epidermal cells were low or absent. Lesional skin samples from patients with psoriasis vulgaris and contact dermatitis contained relatively high numbers of both inflammatory dendritic epidermal cells and plasmacytoid dendritic cells. In contrast, many inflammatory dendritic epidermal cells but only very few plasmacytoid dendritic cells could be detected in atopic dermatitis lesions. Lupus erythematosus was characterized by high numbers of plasmacytoid dendritic cells but low numbers of inflammatory dendritic epidermal cells. These results demonstrate that in addition to resident Langerhans cells, plasmacytoid dendritic cells and inflammatory dendritic epidermal cells are selectively recruited to the skin lesions depending on the type of skin disease. The lack of plasmacytoid dendritic cells in atopic dermatitis may predispose atopic dermatitis patients to viral infections such as eczema herpeticum, a secondary infection of atopic dermatitis lesions with herpes simplex virus. The composition of dendritic cell subsets may help to clarify the etiology of inflammatory skin diseases and forms the basis for therapeutic intervention with selective microbial molecules such as immunostimulatory CpG oligonucleotides.     

Mite allergen induces allergic dermatitis with concomitant neurogenic inflammation in mouse

Pathogenesis of atopic dermatitis involved the interactions of immune and neuroendocrine systems. Here we describe a mouse model for atopic dermatitis with concomitant neurogenic inflammation, by epicutaneous sensitization with a dust mite allergen. Allergen patching resulted in localized dermatitis characterized by pronounced epidermal hyperplasia and spongiosis, which was associated with infiltration of eosinophils and neutrophils, degranulated mast cells, CD4+ and CD8+ T cells, and dendritic cells. There was increased innervation of calcium gene related peptides and substance P in inflamed skins, interactions between nerve fibers and mast cells were seen, indicating the coexistence of neurogenic inflammation. Splenic T cells produced T helper 2-polarized cytokines in response to allergen stimulation in vitro, indicating systemic allergen sensitization. This is the first report of a mouse model of eczema, accompanied by neurogenic inflammation, which shows close resemblance to human allergic diseases. This work supports the notion that the skin is an important site for the initiation of primary allergen sensitization. Besides, this model may also be useful for study of other stress-associated neuroinflammatory skin disorders such as neurogenic pruritus and psoriasis.     

Peripheral natural killer cells exhibit qualitative and quantitative changes in patients with psoriasis and atopic dermatitis

Background Psoriasis and atopic dermatitis are the most recurrent skin inflammatory disorders. Despite their distinct aetiology and clinical aspects, these diseases share several immunological features. Besides the largely documented role of T cells, emerging literature supports a potential involvement of innate immune effectors, the natural killer (NK) cells, in both pathologies. In the peripheral blood, NK cells consist of CD3? CD56dim and CD3? CD56bright cell subsets, harbouring a distinct cell surface phenotype, but both endowed with the main NK‐cell effector functions: cytotoxicity and cytokine production. Objectives To determine whether the frequency, the cell surface phenotype and the functional properties of peripheral NK cells were affected in patients with psoriasis or atopic dermatitis. Methods Peripheral blood mononuclear cells were isolated from 11 patients with psoriasis, nine patients with atopic dermatitis and 16 healthy individuals. By using flow cytometry, we analysed the following parameters of peripheral NK cells: the frequency, the cell surface expression of several NK‐cell receptors (NKR) and the activation of the effector functions upon various in vitro stimuli. Results Peripheral NK cells were significantly reduced in both skin diseases. The cell surface expression of various NKR was differently modified in peripheral NK cells of the two cohorts of patients. Finally, NK‐cell natural cytotoxicity was affected only in atopic dermatitis, while interferon‐γ production was defective in both groups of patients. Conclusion Psoriasis and atopic dermatitis are associated with quantitative and qualitative changes of peripheral NK cells, mostly shared by both diseases, supporting a common process implicating these innate effectors in skin inflammation.     

Stress protects from allergic sensitisation via Substance-P modified antigen presentation

Stress is a potent immunomodulator and aggravator of atopic disease. In a combined murine model of atopic like‐allergic dermatitis (AD) and perceived stress (noise) we previously demonstrated that stress increases Substance P (SP) immunoreactive nerve fiber number and subsequent neurogenic inflammation. Stress also induced an altered Th1/Th2 cytokine balance indicating modulation of antigen presentation. To investigate the effect of stress and SP on dendritic cell‐T cell interaction during allergen sensitisation and the subsequent modification of allergic inflammation, we exposed AD mice to stress prior to sensitisation. Stress markedly increased dendritic cell (DC) migration and maturation in a SP dependent manner. Moreover, the effects of stress were selectively abolished when animals were treated with NK1 antagonist. Interestingly, in stressed AD mice, the number of regulatory CD4⁺CD25⁺ T cells (Tregs) was increased, while other T cell subsets were decreased. When dendritic cells from stressed AD mice were co‐cultured with T lymphocytes we measured higher medium concentrations of TH1 (IFN? and TNF?) vs. TH2 (IL‐4 and IL‐5) cytokines, as well as higher levels of IL‐2 indicating promotion of ‘anti‐allergic’ TH1 and T regulatory phenotypes. Concordantly with the stress and SP dependent alterations in DC‐T cell interaction disease severity (eosinophilic infiltrates, epidermal thickening) was significantly decreased. This reduction in skin inflammation was abrogated in mice treated with NK1 antagonist. Taken together, our data show that via SP‐dependent mechanisms stress may be involved in the sensitisation of atopic individuals to allergen and thereby determine the course of the disease.     

特异性免疫治疗对特应性皮炎T细胞亚群及NK细胞的影响

目的：探讨特异性免疫治疗对特应性皮炎T细胞亚群及NK细胞的影响。方法：采用流式细胞仪检测45例特异性皮炎（atopic dermatitis，AD）患者和30例健康献血员外周血CD3^＋、CD4^＋、CD8^＋T细胞、B细胞、NK细胞的构成比，计算CD4／CD8比值；并比较27例AD患者经特异性免疫（specific immunotherapy，SIT）治疗后T细胞亚群、NK细胞的变化。结果：AD患者CD4^＋、NK细胞构成比、CD4^＋/CD8^＋比值均低于正常对照组（P〈0．05），而CD3^＋、CD8^＋、B细胞与正常组相比差异无统计学意义（P〉0．05）。AD患者经SIT治疗6～18个月后，CD4^＋、NK细胞构成比、CD4^＋／CD8^＋比值均高于治疗前患者，差异有统计学意义（P〈0．05）。结论：AD患者存在细胞免疫功能低下，SIT治疗可显著提高AD患者细胞免疫功能，对AD患者不失为较为有效的对因治疗方法。     

Etiopathogenesis of atopic dermatitis--an overview

Atopic eczema/dermatitis syndrome is a term that covers different subtypes of atopic dermatitis. The "intrinsic" type of atopic dermatitis is non-IgE-associated, and the "extrinsic" type is IgE-associated atopic eczema/dermatitis syndrome. In the etiopathogenesis of atopic dermatitis there are well known interactions among genetic, environmental, skin barrier, immune factors, and stress. Genetic factors determine the expression of atopic dermatitis as pure or mixed with concomitant respiratory or intestinal allergy, depending on genetic susceptibility. Immunologic abnormalities of type I and type IV reactions have been described in patients with atopic dermatitis. Immunologic triggers are aeroallergens, food allergens, microbial products, autoallergens and contact allergens. Immune reactions determine many features of atopic dermatitis. These immune reactions also include cell mediated or delayed hypersensitivity. The currently accepted model proposes a predominant Th2 cytokine milieu in the initiating stages of acute atopic dermatitis lesions, and a mixed Th1 and Th2 pattern in chronic lesions. A two-phase model includes Th2 initiation with attraction of macrophages and eosinophils, which in turn produce interleukin 12 that is the activator of Th1 type response. Atopic dermatitis skin contains an increased number of IgE-bearing Langerhans cells which bind allergens via the high-affinity IgE receptor (FcepsilonRI). Langerhans cells play an important role in cutaneous allergen presentation to Th2 cells via major histocompatibility molecules. Eosinophilia and IgE production are influenced by type 2 cytokines. Degranulation of eosinophils occurs in the dermis with the release of toxic proteins such as major basic protein and could account for much of the inflammation. Mast cells are increased in number and produce mediators other than histamine that induce pruritus and may have an effect on interferon gamma expression. Mast cells produce a number of proinflammatory cytokines. There is an elevated production of prostaglandin E2 by peripheral monocytes. Prostaglandin E2 has at least two potential roles in the initiation of atopic dermatitis. Firstly, it reduces interferon-gamma production by T helper cells, thereby favoring the initial, dominant Th2 immune response; and secondly, it directly enhances IgE production by B lymphocytes with an increased secretion of interleukin 4, interleukin 5 and interleukin 13. Many lesions of atopic dermatitis result from scratching, thus it is tempting to speculate that immune perturbations in genetically predisposed individuals provoke the release of local pruritogens and keratinocyte-derived cytokines, which then further exacerbate the previously described immune response.     

Occupational dermatitis in bakers: a clue for atopic contact dermatitis

6 patients are described who developed contact dermatitis after cereal contact on atopic skin for periods of 2 to 20 years. 2 patients were wheat flour patch-test-positive. They had punch biopsies taken for standard histological and immunohistochemical investigation by labeling with monoclonal antibodies, anti-DR and anti-IgE. Sections showed features of contact dermatitis. There were many dendritic cells located perivascularly in the papilla and in the epidermidis, intensely positive for monoclonal anti-IgE antibody. In control atopic subjects, there were a few perivascular IgE positive cells, probably mastocytes. This study shows that there may be a relationship between some allergens and atopic eczema in patients exposed to them in the course of their work. In some cases, there was a true allergic contact dermatitis, seen through the clinical and histological characteristics, and the results of immunohistochemical study.     

Immunopathologic features of allergic contact dermatitis in humans: participation of plasmacytoid dendritic cells in the pathogenesis of the disease?

Contrary to our abundant knowledge about the sensitization phase of human contact hypersensitivity, little is known about the cell types orchestrating the effector phase. In order to address this issue, we phenotypically analyzed biopsies from 72 h epicutaneous patch test reactions (n=10) and normal human skin (n=5) for the presence of various leukocyte differentiation antigens. The inflammatory infiltrate was dominated by CD3+/CD4+ T cells with approximately 30% of the cells coexpressing CD25 and CTLA-4, a phenotype consistent with either activated effector or regulatory T cells. In our search for professional antigen-presenting cells, we were surprised to find not only sizeable numbers of CD1a+ dendritic cells and CD1c+ dendritic cells, but also of CD123+, CD45RA+, BDCA-2+, CLA+, and CD62L+ plasmacytoid dendritic cells. Although virtually absent in normal human skin, these cells were detectable already 6 h after hapten challenge and were often found in close proximity to CD56+ natural killer cells, indicative of a functional interaction between these cell types. The detailed knowledge of the cellular composition of the inflammatory infiltrate in allergic contact dermatitis and its kinetics should form the basis for the investigation of the immunologic and molecular events operative in the perpetuation and resolution of the eczematous response.     

The HECA-452 epitope is highly expressed on lymph cells derived from human skin

The cutaneous lymphocyte-associated antigen (CLA), recognized by the monoclonal antibody HECA-452, is a cell surface glycoprotein that binds specifically to E-selectin. CLA is present on most T cells at sites of cutaneous immune response and has been shown to be important in lymphocyte homing to the skin. It is expressed only by a minor subset of peripheral T cells and is absent on thymocytes. We have analysed (using a FACScan flow cytometer) the expression of CLA on human lymph cells derived from normal skin, from ultraviolet (UV)-irradiated skin and from allergic contact dermatitis. Whereas in the peripheral blood CLA was expressed on < 20% of CD4 +, CD8 + and CD56 + cells (natural killer cells), > 60% of CD4 +, CD8 + and CD56 + cells isolated from skin-derived lymph expressed CLA. Furthermore, > 90% of CD1a + dendritic lymph cells were positive for CLA. UV irradiation of the skin and induction of an allergic contact dermatitis did not change CLA expression on lymph cells, although lymph flow and cell output increased. These results provide further evidence for an important role of CLA in cell homing to the skin.     

Different in situ distribution patterns of dendritic cells having Langerhans (T6+) and interdigitating (RFD1+) cell immunophenotype in psoriasis, atopic dermatitis, and other inflammatory dermatoses

Dendritic cells bearing Langerhans cell (OKT6+) or interdigitating cell (RFD1+) immunophenotype may be regularly detected within the dermis of chronic skin diseases characterized by a lymphohistiocytic (lymphoreticular) infiltrate. These 2 subsets of antigen-presenting cells within the dermis of lesions of exacerbating chronic plaque psoriasis, exacerbating nummular dermatitis (discoid eczema), atopic dermatitis, allergic contact dermatitis, pityriasis rosea, lichen ruber planus, and cutaneous lupus erythematosus were quantified using computer-assisted morphometry. The mean dendrite length per dermal dendritic cell was significantly higher for RFD1 than for OKT6 (74.4 +/- 0.98 microns vs 70.0 +/- 1.26 microns: p = 0.0023). The mean dendrite length per dermal dendritic cell was remarkably constant for each marker in the various diagnostic categories studied. Disease-specific patterns of total dendrite length and number (expressed per 100 infiltrating mononuclear cells) of these 2 dendritic cell types within the subepidermal infiltrates were obtained. Pityriasis rosea was characterized by its unique high percentage of OKT6+ Langerhans cells. Atopic dermatitis and psoriasis had relatively high percentages of both RFD1+ interdigitating cells and OKT6+ Langerhans cells. Nummular dermatitis had an intermediate number and total dendrite length for OKT6, but was relatively low in RFD1+ cells. Allergic contact dermatitis, lichen planus, and lupus erythematosus had low numbers and dendrite lengths for both dendritic cell subsets. It is suggested that pityriasis rosea is characterized by an abnormal migration pattern of Langerhans cells. Psoriasis and atopic dermatitis may be examples of diseases in which skin-localized antigen-presenting and T-cell-inducing events are continuously taking place. The other diseases may reflect inflammatory processes in which local antigen presentation is less relevant to the tissue reaction.     

马拉色菌相关婴儿皮肤病

马拉色菌是人皮肤表面的常驻真菌，能引起婴儿花斑癣，并与婴儿脂溢性皮炎、婴儿特应性皮炎、新生儿头部脓疱病、婴儿及新生儿痤疮的发病相关。这种相关性主要表现在皮损处能检出马拉色菌，且抗真菌治疗有效，在婴儿特应性皮炎的发病中，主要作为抗原。由于婴儿和新生儿的皮肤屏障功能、机体免疫功能等尚不成熟，在患该类疾病时临床表现不典型，较成人有差异，治疗以外用药物为主。     

Occupational contact urticaria and protein contact dermatitis

Irritant dermatitis and eczema are the most prevalent occupational skin diseases. Less common are immediate contact reactions such as contact urticaria and protein contact dermatitis. Occupational contact urticaria can be subdivided into two categories, immunological and non immunological. However, some agents can induce these two types of reactions. Contact urticaria to natural rubber latex is particularly frequent among health care personnel, but contact urticaria to a wide variety of other substances occurs in many other occupations. Among those at risk are cooks, bakers, butchers, restaurant personnel, veterinarians, hairdressers, florists, gardeners, and forestry workers. Protein contact dermatitis in some of these occupations is caused principally by proteins of animal or plant origin, especially among individuals with a history of atopic dermatitis. Diagnosis requires careful interrogation, clinical examination and skin tests (open tests and prick tests with immediate lecture) to identify a particular contact allergen.     

Contact allergy and allergic contact dermatitis in adolescents: prevalence measures and associations. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS)

The aims of this cross-sectional study were to establish the prevalence measures of contact allergy and allergic contact dermatitis in 8th grade schoolchildren (aged 12-16 years) in Odense, Denmark, and to examine the associations with atopic dermatitis, inhalant allergy and hand eczema. Contact allergy to a standard series allergen was found in 15.2% of schoolchildren. The point prevalence of allergic contact dermatitis was 0.7% and the lifetime prevalence 7.2%, predominantly in girls. The most common contact allergens were nickel (8.6%) and fragrance mix (1.8%). Nickel allergy was clinically relevant in 69% and fragrance allergy in 29% of cases. A significant association was found between contact allergy and hand eczema while no association was found between contact allergy and atopic dermatitis or inhalant allergy. In the future this cohort of schoolchildren will be followed with regard to the course and development of atopic diseases, hand eczema and contact dermatitis. Key words: school-     

Relationship between skin bacterial colonization and the occurrence of allergen-specific and non-allergen-specific antibodies in sera of children with atopic eczema/dermatitis syndrome

In this study we investigated skin bacterial colonization, allergen-specific IgE and antiphospholipid/antinuclear antibodies in 72 children with atopic eczema/dermatitis syndrome (age 2-17 years). Bacteria were found on the skin in 41 cases and serological allergen-specific IgE positivity in 37. The different forms of antibodies appeared in the ratio 21/72 (33 antibodies in 21 children). The occurrence of antiphospholipid antibodies was significantly higher in the patients than in the controls. There were significantly more allergens in the group with bacterial colonization than in the group without colonization. The SCORAD index showed a significant positive association with the skin colonization. We conclude that there are significant relationships between the occurrence of Staphylococcus aureus colonization and the levels of inhalant allergen-specific IgE in children with atopic eczema/dermatitis syndrome, and between the occurrence of antiphospholipid IgM positivity and atopic eczema/dermatitis syndrome.     

Immune dysregulation in atopic eczema.

BACKGROUND--In this review, present knowledge of atopic eczema immunopathogenesis is summarized, emphasizing recent new findings. Systemic abnormalities in cell-mediated immunity have not been demonstrated firmly in patients with atopic eczema. Within the skin itself, there is evidence for decreased cell-mediated immunity, which is partially correlated with the severity of skin disease. Atopic eczema, however, cannot be regarded as a direct result of decreased cutaneous cell-mediated immunity, since immunophenotyping studies have revealed activated T cells as well as dendritic cells within involved skin. In addition, disease marker studies in peripheral blood indicate vigorous T-cell activation in atopic dermatitis. OBSERVATIONS--The original observation of IgE molecules on the membranes of Langerhans cells may indicate trapping of IgE allergen complexes, their processing, and subsequent presentation to allergen-specific T cells within involved skin. Recent findings as to the abnormal regulation of IgE synthesis in atopy point to a preferential expansion of interleukin 4 and interleukin 5 producing allergen-specific T cells, leading to increased production of interleukin 4 and thus increased levels of allergen-specific IgE. We have prepared atopic skin as well as peripheral blood-derived T-cell clones and determined their specificity and cytokine production profile. Results indicate in situ production of interleukin 4 and interleukin 5 within involved skin in response to environmental antigens. CONCLUSIONS--These new findings as to the basis of IgE dysregulation in atopy, as well as to the identification of an abnormal cytokine secretion pattern by T cells presumed to be central in immunopathogenesis of atopy-related disorders, suggest a distorted and cytokine-mediated self-perpetuating response of the skin immune system to environmental allergen(s) in the pathogenesis of skin disease in atopy. These observations may have important implications for the development of new therapies for atopic eczema.     

Blue light irradiation suppresses dendritic cells activation in vitro

Blue light is a UV‐free irradiation suitable for treating chronic skin inflammation, for example, atopic dermatitis, psoriasis, and hand‐ and foot eczema. However, a better understanding of the mode of action is still missing. For this reason, we investigated whether dendritic cells (DC) are directly affected by blue light irradiation in vitro. Here, we report that irradiation neither induced apoptosis nor maturation of monocyte‐derived and myeloid DC. However, subsequent DC maturation upon LPS/IFNγ stimulation was impaired in a dose‐dependent manner as assessed by maturation markers and cytokine release. Moreover, the potential of this DC to induce cytokine secretion from allogeneic CD4 T cells was reduced. In conclusion, unlike UV irradiation, blue light irradiation at high and low doses only resulted in impaired DC maturation upon activation and a reduced subsequent stimulatory capacity in allogeneic MLRs with strongest effects at higher doses.     

In situ quantification of T-lymphocyte subsets and Langerhans cells in the inflammatory infiltrate of atopic eczema

Tissue from the acute, non-infected eruption of sixteen atopic eczema subjects was subjected to an indirect immunoperoxidase technique using monoclonal antibodies recognizing T-lymphocyte subsets, Langerhans cells and natural killer cells. Over half the cells infiltrating the dermis were T lymphocytes, including a large majority of helper T cells and relatively few suppressor T cells. Langerhans cells were present in significant proportions in the dermis and probably reflected increased antigen presentation within the affected skin. There was no evidence of increased natural killer cell presence. This study suggests that type IV hypersensitivity may be implicated in the aetiology of atopic eczema.     

Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases

The capability to take up mannosylated protein antigens is important for the biologic function of dendritic cells, as many glycoproteins derived from bacteria and fungi, e.g., Malassezia furfur, are mannosylated. The expression of the mannose receptor CD206 has been regarded a differentiation hallmark of immature dendritic cells, whereas monocytes and mature dendritic cells as well as epidermal Langerhans cells do not express CD206. This study describes some epidermal dendritic cells that may express CD206 under inflammatory skin conditions: Immunohistochemical and flow cytometric analysis with the CD206-specific D547 antibody confirmed that Langerhans cells from normal human skin do not express CD206. Epidermal cell suspensions from atopic dermatitis and psoriasis revealed two distinct subsets of epidermal dendritic cells: a CD1a(+++)/CD206(-) cell population (i.e., Langerhans cells) and a CD1a(+)/CD206(++) cell population, corresponding to the previously described inflammatory dendritic epidermal cells. CD206-mediated endocytosis, assessed by dextran-fluorescein isothiocyanate uptake, was demonstrated in inflammatory dendritic epidermal cells but not in Langerhans cells. CD206-independent uptake of the fluorescent dye Lucifer yellow, a pinocytosis marker, was demonstrated in both Langerhans cells and inflammatory dendritic epidermal cells. Electron microscopic examination, known to distinguish Langerhans cells from inflammatory dendritic epidermal cells by their Birbeck granules, revealed Langerhans cells with Birbeck granules and inflammatory dendritic epidermal cells without Birbeck granules. Inflammatory dendritic epidermal cells exhibited numerous coated pits and vesicles, the latter fusing with large endosome-like structures, thus suggesting a high endocytotic activity. Immunogold staining with D547 monoclonal antibody confirmed that inflammatory dendritic epidermal cells were positive for CD206. In conclusion, inflammatory dendritic epidermal cells but not Langerhans cells are expressing CD206 in situ and use it for receptor-mediated endocytosis.