IgE-positive epidermal Langerhans cells in allergic contact dermatitis lesions provoked in patients with atopic dermatitis

Summary To see whether or not IgE-bearing epidermal Langerhans cells are specific to skin lesions of atopic dermatitis (AD), we performed immunohistochemical and immunoelectron microscopic examinations of dinitrochlorobenzene (DNCB) contact dermatitis lesions provoked in uninvolved skin of eight patients with AD. In all of the eight examined, IgE-positive epidermal Langerhans cells were observed in the DNCB dermatitis lesions. Typical staining of anti-IgE was absent in the epidermis of normal-appearing skin of five patients with AD. Thus, it is likely that IgE positive epidermal Langerhans cells non-specifically occur in different eczematous diseases provoked in patients with AD.     

In situ expression of the costimulatory molecules CD80 and CD86 on Langerhans cells and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis

Abstract The functional expression of costimulatory molecules on antigen-presenting cells may be a key event in the pathogenesis of atopic dermatitis (AD). Recently, the expression of CD86 (B7-2/B70) has been demonstrated on CD1a⁺ epidermal dendritic cells (DC) in AD lesions by immunohistological and functional analysis. Therefore, we sought to further characterize the in situ expression of costimulatory molecules on these cells, considering the two subpopulations of (1) CD1a⁺⁺⁺/CD11b^– Langerhans cells (LC) containing Birbeck granules and (2) CD1a⁺/CD11b⁺⁺⁺ inflammatory dendritic epidermal cells (IDEC), devoid of Birbeck granules, from AD and other inflammatory skin diseases. Flow cytometry, skin mixed lymphocyte reactions (SMLR) and immunohistological analysis were performed, and showed that IDEC and not LC are the relevant cells expressing the costimulatory molecules CD80 and CD86 in situ. This expression varied with the underlying diagnosis, with AD showing the highest expression of both CD80 and CD86 in situ. Furthermore, the expression of CD80, CD86 and CD36 were significantly correlated. With short-term culture, both CD80 and CD86 were further upregulated on LC and IDEC. Finally, anti-CD86 antibody reduced the stimulatory activity of epidermal DC. These results indicate that costimulatory molecules on LC and IDEC might play a role in the pathogenesis of AD. Received: 7 June 2000 / Accepted: 21 January 2001     

Effects of UVB on fascin expression in dendritic cells and Langerhans cells

BACKGROUND: Fascin is an actin-binding protein that regulates the rearrangement of cytoskeletal elements and their interactions with the cell membrane. Previous studies have indicated that fascin expression is enhanced in DC upon maturation and plays a critical role in T cell activation. Ultraviolet irradiation exerts immunosuppressive effects. OBJECTIVE: We examined the effects of UVB irradiation on the interaction of DC/LC with T cells through fascin. METHOD: Murine bone marrow-derived DC (BM-DC) were induced by recombinant murine GM-CSF and LPS, and UVB irradiation was applied prior to supplementation with LPS. I-A(+) cells (Langerhans cells (LC)) in the epidermal cell suspensions were exposed to UVB irradiation at the beginning of the 24-h culture. BM-DC and LC were analysed by immunohistochemical staining and flow cytometric analyses. To evaluate the effects of UVB irradiation on DC-T cell binding, we examined the clustering of BM-DC with allogeneic CD4(+) T cells under a confocal microscope. RESULTS: Fascin expression in BM-DC and LC was decreased by UVB irradiation. Furthermore, UVB irradiation reduced the ability of BM-DC to cluster with allogeneic CD4(+) T cells. Polarization of fascin and filamentous actin (F-actin) at the point of contact of BM-DC with T cells was also disturbed by UVB irradiation. CONCLUSION: These results suggest that the suppression of fascin expression by UVB irradiation down-regulates the rearrangement of the cytoskeleton and, thereby, antigen presentation in DC/LC.     

Red ginseng for atopic dermatitis

Red ginseng is known for its significant biological activities which include anti-inflammation. Red ginseng may be used for the management and prevention of atopic dermatitis based on its effect on an atopic dermatitis animal model. More therapeutic efficacies other than atopic dermatitis are also reviewed briefly.     

Natural killer cell activity in atopic dermatitis

Summary Natural killer (NK) cell activity against K562 cells was studied in 12 male adults with atopic dermatitis (AD). In a 4-h chromium relase microcytotoxicity assay normal NK cell function and its augmentation by interferon (IFN-alpha) were observed in AD patients. Slightly higher NK cell activity was observed in patients with allergic respiratory symptoms. The role of NK cells in the pathogenesis of atopic dermatitis is discussed.Supported by Oy Star Ab and a grant from the Foundation for Allergy Research (Allergiatutkimussäätiö), Finland     

The presence of IgE molecules on epidermal langerhans cells in patients with atopic dermatitis

Summary Skin sections of clinically involved and clinically normal-looking skin from patients with atopic dermatitis were incubated with anti-human IgE antibodies using the indirect immunoperoxidase technique. Apart from positive dermal anti-IgE staining, positive epidermal anti-IgE staining was also observed. The morphology of the epidermal staining cells suggested the involvement of dendritic cells. This was confirmed by positive immuno-double labelling with OKT6 and anti-IgE. This phenomenon seemed to be specific for atopic dermatitis since skin sections from normal nonatopic controls, patients with allergic asthma, contact dermatitis, and schistosomiasis showed no epidermal anti-IgE staining. To further elucidate the nature of the epidermal anti-IgE staining cells, epidermal cell suspensions were prepared from clinically involved skin from patients with atopic dermatitis. These cell suspensions also showed positive anti-IgE staining cells and positive immuno-double labelling with OKT6 and anti-IgE. Immunogold electron microscopy with anti-IgE on epidermal cell suspensions from patients with atopic dermatitis showed gold particles on the cell membranes of cells containing Birbeck granules, being Langerhans' cells. Epidermal cell suspensions from normal non-atopic controls were negative. The presence of IgE molecules on epidermal Langerhans' cells, which seems to be specific for patients with atopic dermatitis, provides an explanation for the high frequency of positive patch test reactions to inhalant allergens.     

异位性皮炎的记忆性T细胞浸润及ICAM－1表达

为了解粘连分子在异位性皮炎（ＡＤ）炎症及免疫反应过程中的作用，对ＡＤ皮损部位细胞间粘连分子－１（ＩＣＡＭ－１）的表达作了研究。结果虽然正常皮肤表皮不表达ＩＣＡＭ－１，但ＡＤ皮损处角朊细胞则局灶性表达ＩＣＡＭ－１，尤其在有严重单个核细胞浸润及表皮内淋巴细胞移入的部位。免疫表型研究表明，ＡＤ真皮浸润中ＣＤ４＋／ＣＤｗ２９＋／ＣＤ４５ＲＡ－记忆性Ｔ细胞占主导，推测它们可能通过分泌某些细胞因子而诱导角朊细胞表达ＩＣＡＭ－１。ＩＣＡＭ－１与淋巴细胞表面的淋巴细胞功能相关抗原－１（ＬＦＡ－１）之间相互作用可能对淋巴细胞在皮肤内的运行起调控作用。     

Cytokine expression and antigen-presenting capacity of 4F7+ dendritic cells derived from dermis, spleen, and lymph nodes

We took advantage of the recently generated 4F7 mAb, which recognizes an epitope expressed on dendritic cells (DC) from different tissues, to freshly isolate and positively sort for these cells and to characterize their cytokine pattern and antigen-presenting capacity in comparison with epidermal Langerhans cells (LC). RT-PCR and Northern blot analyses demonstrated constitutive mRNA expression of MIP-1γ, MIP-1α, C10, and IL-1β in both 4F7 ⁺ DC and LC. Lipopolysaccharide (LPS) treatment resulted in the upregulation of mRNA expression of all four cytokines and in a newly detected signal for TNFα. Immunoblot analysis showed constitutive secretion of MIP-1γ, with LPS treatment resulting in the upregulation of IL-1β production and in newly detected TNFα secretion. 4F7 ⁺ DC were also shown to express mRNA for the common γ chain receptor of IL-2 and for the receptor of IL-4. Finally, we demonstrated freshly isolated 4F7 ⁺ DC to be equivalent to freshly isolated LC in their capacity to present alloantigen in the mixed leukocyte reaction (MLR) and to process and present purified protein derivative (PPD) to Th1 and Th2 clones. We conclude that 4F7 is a useful marker for positively sorting DC from dermis, spleen, and lymph nodes. Regardless of tissue source, 4F7 ⁺ DC exhibit uniform cytokine and antigen-presenting capacity profiles that mimic the properties of freshly isolated epidermal LC. Received: 15 April 1996     

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out at the site of each biopsy. After fixation and plastic embedding, the biopsies were cut into 2 μm serial sections. Ten sections, 30 μm apart, from each biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were determined. The study yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found in specimens from the neck, (3) staining with toluidine blue yielded a lower number of mast cell profiles than Giemsa staining, (4) the use of Carnoy’s fixative resulted in a lower mast cell profile count than the use of formaldehyde, and (5) there was no statistically significant correlation between the clinical score and the number of mast cell profiles per millimetre squared. Using stereological techniques, this study indicated that mast cells might participate in the inflammatory process in skin leading to atopic dermatitis. Received: 17 April 1996     

Mast cell chymase is increased in chronic atopic dermatitis but not in psoriasis

Mast cell chymase is a chymotrypsin-like serine proteinase primarily stored in secretory mast cell granules. Mast cell chymase has various effects on angiotensin, metalloproteases, lipoproteins, procollagen, neuropeptides and cytokines. Recent studies have demonstrated that chymase inhibitors inhibit skin inflammation. In this study we sought to determine the role of mast cell chymase in atopic dermatitis (AD) in comparison with its role in psoriasis and normal skin. Skin biopsy specimens were obtained from non-lesional and lesional skin of patients with chronic AD and psoriasis and from normal skin of non-atopic and non-psoriatic controls. The number of mast cells containing chymase was determined by immunohistochemistry using a chymase-specific monoclonal antibody. A significantly (P<0.05) enhanced number of chymase-positive cells was found in lesional AD skin as compared to normal skin as well as to lesional and non-lesional skin of patients with psoriasis. A significant (P<0.05) increase in the number of chymase-positive cells was also found in non-lesional AD skin in comparison to psoriasis. An enhanced, albeit not statistically significant difference was noted in non-lesional AD skin as compared to normal skin. In conclusion, these results suggest that mast cell chymase may play an integral part in eliciting and maintaining cutaneous inflammation in AD but not in psoriasis. The increased proteinase activity of mast cell chymase may also be involved in promoting a skin barrier defect in AD, which subsequently enhances the skins permeability to allergens and microbes and thereby aggravates the eczema.     

A low level of health literacy is a predictor of corticophobia in atopic dermatitis

BackgroundTopical corticosteroids (TCS) are the mainstay of treatment in atopic dermatitis (AD) flares. The fears and worries concerning TCS are known as corticophobia. Corticophobia is common in patients with AD and can lead to suboptimal TCS application and treatment failure. Health literacy (HL) may influence corticophobia. TOPICOP© and HLS-EU-PT questionnaires have been developed to evaluate corticophobia and HL, respectively.ObjectiveEvaluate the relationship between corticophobia and the degree of HL in patients with AD.MethodsProspective cross-sectional study with AD patients followed at a Dermatology Department, between September 2019 and February 2020. Patients, or their parents (if patients had ≤ 15 years), were invited to answer TOPICOP© questionnaire, HLS-EU-PT questionnaire, and a disease characterization and demographic questionnaire.ResultsWe included 61 patients (57.4% females, mean age 20 ± 13.8 years, mean disease duration of 12.5 ± 11.4 years). TOPICOP© mean score was 44.8 ± 20.0 (8.3 to 88.9) and HLS-EU-PT mean score was 30.5 ± 8.5 (1.1 to 47.9). TOPICOP© score was negatively correlated with HLS-EU-PT score (p = 0.002, r = -0.382,  r² = 0.146). There was no statistical difference between TOPICOP© score and disease characteristics (disease severity, family history of AD or personal history of other atopic diseases).Study limitationsSmall and heterogenous cohort composed of patients and patients’ parents.ConclusionThe degree of corticophobia is similar to the values reported in other studies. HL had an inverse correlation with corticophobia. Lower HL was shown to be a predictor of higher corticophobia. The promotion of health literacy is essential for the correct use of TCS and good control of AD.     

树突细胞在特应性皮炎发病中的研究进展

特应性皮炎是一种慢性复发性炎症性皮肤病,具有血清IgE水平升高、Th2型免疫过度反应以及对多种病原微生物易感性增加等特点.研究表明,朗格汉斯细胞和表皮炎症样树突细胞是在特应性皮炎皮损中出现的两种树突细胞.其中表皮炎症样树突细胞是炎症性皮肤病所特有的一种树突细胞,仅在炎症性皮肤中表达,被激活后可释放大量炎症因子和趋化因子,而在皮炎得到成功控制后逐步消失.在特应性皮炎的病理生理机制中,表皮炎症样树突细胞不仅在炎症的持续和发展中起着重要作用,还可能与皮损局部Th2反应向Thl反应漂移有关.     

肥大细胞在特应性皮炎发病中的研究进展

特应性皮炎是一种与遗传过敏素质有关的慢性、复发性、瘙痒性、炎症性皮肤疾病，其病因复杂，发病机制尚未明确。近年来，随着对特应性皮炎直接相关的效应细胞及效应分子，特别是肥大细胞及其表达的细胞因子的深入研究，逐步明确肥大细胞在特应性皮炎炎症过程中迁移、聚集、局部数量增多的机制，以及肥大细胞与嗜酸粒细胞、T细胞之间相互作用的关系。其结果将有助于进一步理解特应性皮炎皮肤炎症的细胞基础，并可能为临床治疗提供新的靶点。     

辅助性T细胞17/调节性T细胞失衡与特应性皮炎的研究进展

特应性皮炎多见于婴幼儿期发病.其病因不明,发病机制复杂.目前认为,特应性皮炎的病因和发病机制与多种免疫细胞相关.辅助性T细胞17/调节性T细胞是近年来发现的一对具有相反功能的CD4+T细胞亚群.辅助性T细胞17介导炎症反应,与多种自身免疫性疾病关系密切相关,调节性T细胞可以抑制T细胞介导的炎症反应,维持免疫耐受,可以预防自身免疫性疾病的发生.辅助性T细胞17/调节性T细胞失衡在特应性皮炎等多种炎症性、自身免疫性疾病中发挥着重要作用.     

卡介菌多糖核酸对Nc/Nga小鼠特应性皮炎的保护作用

目的 探讨卡介菌多糖核酸（BCG-PSN）对Nc/Nga小鼠特应性皮炎皮损的预防作用及可能机制。 方法 外用二硝基氯苯（DNCB）反复刺激新生Nc/Nga小鼠,通过皮炎评分、搔抓行为、组织病理学、免疫学指标评价皮炎损伤程度,观察BCG-PSN对小鼠皮损的预防作用。 结果 出生后4周内重复注射BCG-PSN,可以显著改善DNCB致敏Nc/Nga小鼠皮损炎症程度,降低皮炎评分以及小鼠的搔抓行为,不同浓度BCG-PSN组之间搔抓频率差异无统计学意义。BCG-PSN可以降低血浆中IgE的含量,呈剂量依赖性。0.5 mg/kg BCG-PSN可增加皮损中分泌干扰素（IFN）γ的细胞数量。不同剂量BCG-PSN均可降低脾单一核细胞培养上清液中IL-4的含量,增加IL-12的浓度。 结论 早期注射BCG-PSN可通过促进分泌IFN-γ的细胞增生,增加IL-12合成,降低IL-4和IgE的含量,从而预防Nc/Nga小鼠皮炎发生。     

sIL-2R及IgE在异位性皮炎患者血清中的测定

为了探讨异位性皮炎（ＡＤ）的发病机理,了解血清可溶性白细胞介素２受体（ｓＩＬ２Ｒ）在ＡＤ患者血清中的意义,对４７例ＡＤ患者作了血清ｓＩＬ２Ｒ及ＩｇＥ检测,并对１１例患者在治疗好转后予以复查。结果显示,ＡＤ患者的血清ｓＩＬ２Ｒ显著高于正常对照组（Ｐ＜０００１）,但与ＡＤ的严重程度无显著关系（Ｐ＞００５）。其中１１例患者经治疗后病情显著好转（Ｐ＜０００１）,而血清的ｓＩＬ２Ｒ仍无显著下降（Ｐ＞００５）。