CCL27、CCR10在鲍温病患者皮损中的表达

目的:比较CCL27、CCR10在鲍温病患者皮损及正常皮肤中的表达水平,并分析其与鲍温病发病的联系。方法:采用免疫组化染色SABC法检测14例鲍温病患者组织和7例正常皮肤中CCL27、CCR10的表达。结果:鲍温病患者皮损中,CCL27、CCR10的表达水平明显高于正常皮肤(t=-4.34,P<0.01;t=-12.32,P<0.01),CCL27、CCR10的表达水平差别明显小于正常皮肤(t=4.20,P<0.01)。结论:CCL27、CCR10在鲍温病患者皮损中的高表达可能与鲍温病发病密切相关。     

CCL27及其受体在银屑病血清和皮损中的表达

目的:检测趋化因子CCL27及其受体CCR10在银屑病患者血清和皮损中的表达.方法:采用ELISA方法检测40例银屑病患者血清CCL27水平,并采用免疫组化SP法检测其中25例患者皮损和15例正常人皮肤中CCL27和CCR10的表达情况.结果:(1)银屑病患者血清CCL27水平(799.94±214.54)pg/mL,高于健康人对照组(373.10±92.84)pg/mL,P<0.001.(2)在寻常型银屑病患者皮损,CCL27强烈表达于皮肤基底层至颗粒层,CCR10表达于真皮浅层淋巴细胞,表达阳性率明显高于正常人皮肤(P<0.001).结论:CCL27与受体CCR10相互作用,参与了银屑病的发病.     

Decrease in circulating Th17 cells correlates with increased levels of CCL17, IgE and eosinophils in atopic dermatitis

Background

Clinical significance of circulating CD4⁺ T cell subsets, including T-helper (Th)1, Th2, Th17 and regulatory T (Treg) cells, in patients with atopic dermatitis (AD) remains unclear. No previous studies have simultaneously evaluated the four T cell subset profiles in AD.

Objective

The aim of the present study was to explore whether the percentage of these four subsets of CD4⁺ T cells correlate to the severity parameters of AD patients.

Methods

Intracellular expression of interferon (IFN)-γ, interleukin (IL)-4, IL-17 and forkhead box P3 (Foxp3) in CD4⁺ T cells was evaluated in peripheral blood mononuclear cells from normal controls and patient with AD as well as with chronic eczema using a flow cytometer. Serum CCL17 levels were measured as an objective severity parameter of AD together with percentage of eosinophils and serum IgE levels.

Results

In AD patients, the number of Th1 (IFN-γ⁺) and Th17 (IL-17⁺) subsets was significantly decreased, but that of Th2 (IL-4⁺) and Treg (Foxp3⁺) subsets was similar to that of normal controls. The T cell subset profiles of patients with chronic eczema were not different with those of normal controls. The frequency of Th17cells, particularly that of the IFN-γ^negaIL-17⁺ subset, showed a significant negative correlation with CCL17, IgE and eosinophil levels in AD patients. This was, however, not the case in Th1, Th2 and Treg cells.

Conclusion

Decreased circulating Th17 cells might contribute to activity of AD.     

TLR2 and TLR4 expression in atopic dermatitis,contact dermatitis and psoriasis

The aim of the study was to investigate the expression of Toll‐like receptors (TLRs) 2 and 4 on keratinocytes in atopic dermatitis, contact dermatitis, and psoriasis by PCR and by immunohistochemistry including confocal microscopy. Confocal microscopy revealed a granular intra‐cellular expression pattern for TLR 2 and a homogenous intra‐cellular expression pattern for TLR 4 in normal and diseased skin. TLR 2 was constitutively expressed in the suprabasal layers in normal skin, but limited to the basal epidermis in diseased skin. TLR 4 expression was concentrated to the basal layers in normal skin, whereas it was pronounced in upper layers in diseased skin. The shift in the TLR expression may be related to the disturbed skin barrier and a need for enhanced immune surveillance because of invading microbes. Also, there must be a balance between sufficient immune response and overstimulation.     

趋化因子CCL27在常见炎陛皮肤病中的作用

临床常见的炎性皮肤病,如,银屑病、特应性皮炎和接触性皮炎等,其典型特征是T淋巴细胞浸润为主的皮肤炎症。趋化因子CCL27主要由皮肤角质形成细胞产生,其惟一受体是CCRl0。CCL27和CCRl0的相互作用,诱导皮肤记忆T细胞向局部皮肤的聚集,形成并维持了各种炎性皮损,因而已成为药物研究的新靶点。尽管目前尚无真正的临床药物可用,但体外研究和动物实验的良好效果为炎性皮肤病的治疗开启了一扇新的大门。     

CCL20、CCR6及IL-17A在寻常型银屑病患者血清中的表达及意义

目的观察趋化因子CCL20及其受体CCR6、白细胞介素(IL)-17A在银屑病患者血清中的变化,并探讨其在银屑病发病中的作用。方法采用酶联免疫吸附法测定26例斑块型、7例点滴型银屑病患者及8名健康人血清中CCL20、CCR6及IL-17A的浓度,并对银屑病皮损面积和严重程度指数(PASI)评分、病程进行相关性分析。结果斑块型银屑病患者血清CCL20、CCR6及IL-17A浓度(748.74±268.72,10.20±3.75,39.22±13.21)均显著高于健康对照组(578.45±204.93,6.79±4.61,25.54±13.04)(P分别0.05,0.01,0.01)。点滴型银屑病与对照组差异无统计学意义。CCL20、CCR6与PASI评分呈正相关(r=0.416,r=0.350)(P0.05)。CCL20、CCR6及IL-17A三者之间均存在显著正相关(r=0.852,r=0.801,r=0.825)(P0.001),与病程无明显相关性。结论 CCL20、CCR6及IL-17A参与斑块型银屑病的病理过程。     

A novel molecular disease classifier for psoriasis and eczema

Novel specific therapies for psoriasis and eczema have been developed, and they mark a new era in the treatment of these complex inflammatory skin diseases. However, within their broad clinical spectrum, psoriasis and eczema phenotypes overlap making an accurate diagnosis impossible in special cases, not to speak about predicting the clinical outcome of an individual patient. Here, we present a novel robust molecular classifier (MC) consisting of NOS2 and CCL27 gene that diagnosed psoriasis and eczema with a sensitivity and specificity of >95% in a cohort of 129 patients suffering from (i) classical forms; (ii) subtypes; and (iii) clinically and histologically indistinct variants of psoriasis and eczema. NOS2 and CCL27 correlated with clinical and histological hallmarks of psoriasis and eczema in a mutually antagonistic way, thus highlighting their biological relevance. In line with this, the MC could be transferred to the level of immunofluorescence stainings for iNOS and CCL27 protein on paraffin‐embedded sections, where patients were diagnosed with sensitivity and specificity >88%. Our MC proved superiority over current gold standard methods to distinguish psoriasis and eczema and may therefore build the basis for molecular diagnosis of chronic inflammatory skin diseases required to establish personalized medicine in the field.     

β趋化因子CCL20及其受体CCR6mRNA在寻常性银屑病患者皮损中的表达

目的探讨β趋化性细胞因子家族中CC趋化因子配体20(CCL20)及其受体CC趋化因子受体6(CCR6)mRNA在寻常性银屑病患者皮损中的表达情况.方法应用逆转录-聚合酶链式反应(RT-PCR)方法检测35例寻常性银屑病患者皮损和18例正常人皮肤中CCL20和CCR6mRNA的表达.结果与正常人皮肤相比,寻常性银屑病患者皮损中CCL20与CCR6mRNA的表达水平均明显增高(P＜0.001).结论寻常性银屑病患者皮损中CCL20和CCR6 mRNA表达水平的上调可能与银屑病的发病有关.     

CTACK /CCL27 expression in psoriatic skin and its modification after administration of etanercept

BACKGROUND: Tumour necrosis factor-alpha upregulates the expression of a cutaneous T cell-attracting chemokine (CTACK/CCL27), that promotes migration of cutaneous lymphocyte-associated antigen-positive lymphocytes into the skin. The role of CTACK/CCL27 in pathogenesis of psoriasis has recently been documented but no data are available at the present time on its modification in psoriatic cutaneous tissue after administration of etanercept. OBJECTIVES: To evaluate modifications of CTACK/CCL27 expression in skin of patients with psoriasis after administration of etanercept and their relation with disease activity. METHODS: Twenty-two patients with moderate to severe psoriasis underwent clinical, histological and immunohistochemical evaluations of disease activity at baseline and at 12 and 24 weeks after starting treatment with etanercept. RESULTS: All selected patients experienced an improvement of Psoriasis Area and Severity Index (PASI) score (P < 0.001) and Dermatology Life Quality Index score (P < 0.001) during the treatment. Skin histological abnormalities showed statistically significant modifications during treatment (P < 0.001). Immunohistochemical expression of CTACK/CCL27 decreased significantly (P < 0.001) and its relation with final PASI score was statistically significant (P < 0.05); the pattern of distribution of CTACK/CCL27 immunoreactivity significantly moved from diffuse and predominantly suprabasal to basal (P < 0.001) and the restoration of basal distribution of CTACK/CCL27 was also significantly related to clinical improvement of cutaneous disease (P < 0.001). CONCLUSIONS: Etanercept induces a clinical and histological improvement of psoriatic disease, promoting a reduction in CTACK/CCL27 cutaneous immunostaining and favouring the restoration of physiological CTACK/CCL27 epidermal expression. Moreover, CTACK/CCL27 reduction in cutaneous expression during administration of etanercept could be considered a favourable prognostic marker.     

Expression of the T-helper 2-specific chemokine receptor CCR4 on CCR10-positive lymphocytes in atopic dermatitis skin but not in psoriasis skin

BACKGROUND: Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases. AD is generally perceived as a T-helper (Th) 2-dominated disease whereas psoriasis is a Th1-dominated disease. The chemokine cutaneous T-cell attracting chemokine (CTACK) and its receptor CCR10 attract skin-homing lymphocytes to inflamed skin, suggesting that CCR10+ cells in AD and psoriasis should be of Th2 and Th1 type, respectively. The chemokine receptor CCR4 is expressed selectively on Th2 lymphocytes and its ligand thymus and activation-regulated chemokine (TARC) is upregulated in AD lesions, suggesting that the CCR10+ cells in AD lesions should also express CCR4. OBJECTIVES: To examine the coexpression of CCR10 and CCR4 on skin-invading lymphocytes in AD and psoriasis lesions as well as the Th1/Th2 cytokine expression of the CCR10+ lymphocytes. METHODS: Skin biopsies from AD and psoriasis patients were double stained with antibodies against CCR10-CCR4, CCR10-CCR5, CCR10-interleukin (IL)-2 and CCR10-IL-4. RESULTS: The CCR10+ cells in AD showed a mixed IL-2/IL-4 expression pattern, and a minor proportion expressed CCR4, whereas a large proportion of the CCR4+ cells did not express CCR10. In psoriasis the CCR10+ cells only expressed IL-2, and no CCR4 expression was detected. CONCLUSIONS: The CCR10+ lymphocytes invading the skin in AD and psoriasis have different Th1/Th2 profiles, as measured by both their cytokine and chemokine receptor expression. This suggests that the CCR10+ subpopulation of lymphocytes is made up of different Th1/Th2 subsets. However, the Th1/Th2 lymphocytes of AD and psoriasis were either CCR10+ or CCR10-, suggesting that both the Th1 and Th2 subpopulation can be subdivided further. CCR4 was found only in AD skin and on both CCR10+ and CCR10- cells, supporting the hypothesis of TARC and CTACK as being independent lymphocyte-attracting chemokines in AD.     

Statins inhibit chemotactic interaction between CCL20 and CCR6 in vitro: possible relevance to psoriasis treatment

Psoriasis is a chronic IL-23/Th17 pathway-associated skin disease. An increased expression of lesional CCL20 can recruit CCR6+ Th17, and lesional cytokine milieu persistently activates keratinocytes to produce CCL20. Lipid-lowering drugs, statins, are known to possess immune-modulating functions. In this study, we explored an inhibitory effect of statins on CCL20/CCR6 interaction. We demonstrated that IL-1β, TNF-α, and IL-17A significantly increased CCL20 production from HaCaT cells. However, these increments were markedly inhibited by fluvastatin and simvastatin, but not by pravastatin. In the chemotaxis migration assay, pretreatment with fluvastatin and simvastatin inhibited the migration of human CD4+ T cells towards CCL20. However, the level of CCR6 surface expression in memory CD4+ T cells was not affected. Our results suggest that not all, but specific types of statins may be of benefit in alleviating psoriasis partially via interrupting CCL20/CCR6 chemotactic interaction, the mechanism which may eventually lessen the infiltration of Th17 cells.     

Increased expression of CC chemokine ligand 18 in extrinsic atopic dermatitis patients

Background:  Although most patients with atopic dermatitis (AD) show high total and allergen-specific serum immunoglobulin E (IgE) levels, a small subgroup of AD patients have normal total IgE levels and negative serum allergen-specific IgE. This subgroup has been termed 'intrinsic' AD (IAD) as a counterpart to 'extrinsic' AD (EAD). However, the difference of chemokines between IAD and EAD has not yet been evaluated.
Objective:  We investigated the expression of CC chemokine ligand (CCL) 17, CCL22, and CCL18 in patients with IAD and EAD, which are known to be highly expressed in AD patients.
Methods:  We assessed the protein levels of these chemokines in peripheral blood mononuclear cells (PBMCs), sera and lesional skins. We also evaluated CCL18 mRNA levels in monocytes, Langerhans cell (LC)-like dendritic cells (DCs) and inflammatory dendritic epidermal cell (IDEC)-like DCs from both types of AD patients.
Results:  There were no significant differences in CCL17 and CCL22 expression in PBMCs, sera and lesional skins of patients with IAD and EAD. CCL18 expression did not differ in PBMCs, sera and LC-like DCs from the two subgroups, but strong CCL18 expression was observed in lesional skins and IDEC-like DCs in patients with EAD. Lastly, serum CCL18 levels significantly decreased after immunotherapy.
Conclusion:  This study suggests that the chemokine micromilieu, especially the level of CCL18, is different between EAD and IAD patients. High FcεRI surface-expressing DCs, such as IDEC, were the major source of CCL18, and produced a prominent CCL18 microenvironment in EAD patients compared with IAD patients.     

特应性皮炎患者外周血辅助性T细胞17与白介素17的检测

目的 探讨特应性皮炎（atopic dermatitis,AD）患者外周血白介素17蛋白和mRNA水平及辅助性T细胞17（Th17）表达及其意义。方法 用酶联免疫吸附测定法（ELISA）检测63例AD患者及30例正常人对照血浆中IL-17蛋白水平。实时荧光定量RT-PCR检测两组外周血中IL-17 mRNA表达水平。流式细胞仪检测AD患者和对照者外周血单一核细胞中Thl7细胞的比例。分析外周血Th17细胞比例和IL-17水平与AD患者病情严重度的相关性。结果 急性期AD患者外周血中Th17细胞比例为1.83% ± 0.47%,明显高于正常人对照组（0.85％ ± 0.45％,t = 4.128,P < 0.01）和慢性期组（1.12% ± 0.69%,t = 2.439,P < 0.05）。AD组外周血中血浆IL-17水平为98.37 ng/L,高于正常人组63.75 ng/L,U = 168,P < 0.05。AD组外周血IL-17mRNA表达水平高于正常人对照组。AD患者外周血Th17细胞比例和血IL-17蛋白水平与湿疹面积及严重度指数（EASI）积分均呈显著正相关（r = 0.68l,P < 0.01;r = 0.427,P < 0.05）。结论　急性期AD患者外周血Th17细胞比例显著升高, IL-17蛋白分泌及基因表达水平存在异常,与病情严重度明显相关,提示IL-17和Th17细胞可能在AD发病中起作用。     

Role of chemokines and the corresponding receptors in vitiligo: A pilot study

To determine the levels and sources of chemokines in the serum and epidermis of vitiligo patients, we examined 80 active patients, 80 stable patients and 40 healthy controls. First, the serum levels of candidate chemokines were measured by Luminex assay, and levels of CCR5, CXCR1 and CXCR3 were measured in peripheral mononuclear cells (PMBC) by flow cytometry. Then, the local epidermis levels of elevated chemokines in vitiligo were tested by Luminex. Finally, the mRNA and protein expression levels of elevated chemokines in HaCaT cells stimulated with interferon (IFN)‐γ or tumor necrosis factor (TNF)‐α were tested by quantitative real‐time polymerase chain reaction and Luminex. The serum levels of CCL5, CXCL8 and CXCL10 in active vitiligo were significantly elevated compared with those in stable vitiligo patients. Furthermore, the levels of CCL3 and CCL4 had weak and positive correlations with the Vitiligo Area Scoring Index. In the peripheral blood of active vitiligo patients, the percentages of CD3⁺CD8⁺CCR5⁺ and CD3⁺CD8⁺CXCR3⁺ T cells were significantly increased compared with those in stable vitiligo and healthy controls. In the epidermis of lesions, the expression levels of CCL5 and CXCL10 in active vitiligo were significantly increased. In addition, the mRNA and protein levels of CCL5, CXCL8 and CXCL10 were significantly elevated in HaCaT cells after stimulation with TNF‐α or IFN‐γ. The CCR5/CCL5 and CXCR3/CXCL10 axes may play an important role in the progression and maintenance of vitiligo. Moreover, keratinocytes stimulated with TNF‐α and IFN‐γ may be a primary source of CCL5 and CXCL10.     

Dermoscopy in differential diagnosis of palmar psoriasis and chronic hand eczema

Clinical differentiation between palmar psoriasis and chronic hand eczema may sometimes be a diagnostic challenge; in such cases histopathological analysis helps to differentiate the two conditions. In the present study, palmar psoriasis and chronic hand eczema were investigated using dermoscopy and the significance of specific dermoscopic features was assessed in order to improve their non‐invasive differentiation. Ten patients with biopsy‐proven palmar psoriasis and 11 patients with biopsy‐proven chronic hand eczema were included in the study. We found that the presence of diffuse white scales was significant in palmar psoriasis whereas the presence of yellowish scales, brownish‐orange dots/globules and yellowish‐orange crusts was significant in chronic hand eczema.     

TARC与CCR4在特应性皮炎患者外周血中的表达

目的:检测胸腺和活化调节趋化因子(TARC)与其受体CCR4在特应性皮炎(AD)外周血中的表达.方法:酶联免疫吸附法检测45例AD患者及30名正常人血清TARC水平;流式细胞仪检测外周血单核细胞CCR4的表达.结果:AD患者血清TARC水平为(1169.1±106.5)pg/mL,显著高于对照组(337.3±45.6)pg/mL的水平(P<0.01).CCR4表达水平为(60.1± 2.4)%,较对照组显著升高(P<0.01);TARC和CCR4表达水平均与疾病严重程度呈正相关(均P<0.01).结论:TARC与CCR4在AD的发病机制中可能起一定作用.