CD40 expression on antigen presenting cells and correlation with disease severity in atopic dermatitis

CD40 expression on antigen presenting cells and correlation with disease severity in atopic dermatitis
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DOI:
10.1684/ejd.2008.0495
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发表时间:
2008-09-01
影响因子:
2.5
通讯作者:
Gerber, Hans-Peter
Gerber, Hans-Peter
中科院分区:
医学4区
文献类型:
--
作者:
Oflazoglu, Ezogelin;Simpson, Eric L.;Gerber, Hans-Peter

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特应性皮炎(AD)是一种慢性炎症性皮肤病,与皮肤对环境刺激的高反应性有关,导致炎症细胞浸润增加,IgE产生增加,各种共刺激分子、Th2细胞因子和趋化因子表达增强。抗原呈递细胞(APCs)在AD疾病的发病机制中起着至关重要的作用,APCs与炎症T细胞之间的相互作用是诱导和维持炎症过程所需的重要信号。在特应性皮炎患者中,CD40在炎症细胞上表达上调;然而,这些细胞的身份及其与疾病严重程度的相关性尚不清楚。为了解决这些问题,我们检测了AD患者皮肤病变和外周血细胞中的CD40表达,并发现CD40阳性细胞数量与疾病严重程度呈正相关。此外,我们确定了皮肤病变中CD40阳性细胞的性质,包括CD1a(+)和cdi I b(+) apc。最后,我们发现血清PARC和IgE水平与AD皮损中CD40(+)细胞数量之间存在相关性。综上所述,这些发现表明CD40在apc上上调,而apc是先前被证明与AD疾病病理有关的细胞类型,并表明靶向CD40阳性细胞的治疗策略可能对AD患者有益。
Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental stimuli, resulting in increased infiltration of inflammatory cells, IgE production and enhanced expression of various co-stimulatory molecules, Th2 cytokines and chemokines. Antigen presenting cells (APCs) are critical for AD disease pathogenesis and interaction between APCs and inflammatory T cells represents an important signal required for induction and maintenance of the inflammatory process. CD40 was shown to be upregulated on inflammatory cells in patients with atopic dermatitis; however the identity of these cells and their correlation with disease severity remained unknown. To address these questions, we determined CD40 expression in skin lesions and on peripheral blood cells from AD patients and identified a positive correlation between the numbers of CD40 positive cells and disease severity. Furthermore, we identified the nature of CD40 positive cells in skin lesions to include CD1a(+) and CD I I b(+) APCs. Finally, a correlation between serum PARC and IgE levels and the numbers of CD40(+) cells in AD skin lesions was found. Combined, these findings demonstrate that CD40 is upregulated on APCs, cell types previously shown to contribute to AD disease pathology, and suggest that therapeutic strategies targeting CD40 positive cells may provide benefit to AD patients.