Analysis of altered function of dendritic cells from atopic dermatitis or psoriatic patients

特应性皮炎(AD)的特征是在皮肤和外周血中存在Th2型细胞，尽管在AD的慢性皮肤皮损中也有报道以干扰素-γ(干扰素-γ)产生细胞为主。最近发现，Th1或Th2的发育受到抗原提呈细胞(APC)产生的因素的强烈影响。为了阐明AD患者的APC在Th2细胞分化中是否起到有利的作用，我们比较了13例AD患者和13例年龄匹配的健康对照组单核细胞(MO)和单核细胞来源的DC(MoDC)在不同试剂刺激下产生细胞因子和表达共刺激分子的情况。检测IL-1β、IL-10、IL-12p40、IL-12p70的产生及CD23、CD40、CD54、CD80、CD83、CD86、HLADR的表达。我们用超抗原、脂多糖、激动型抗CD_(40)抗体、植物血凝素、IL-1β/肿瘤坏死因子-α、IL-4或干扰素-γ刺激它们。结果表明：1)内毒素刺激后，AD-MOS产生IL-10的能力明显增强。相反，经各种刺激后，AD-MOS组IL-12p40的产生明显低于HC-MOS组。2)内毒素刺激后AD MODC中IL-12p40的表达也明显降低。3)IL-4对AD患者CD23的诱导作用明显增强。这些结果表明，AD APC在脂多糖、IL-1β/肿瘤坏死因子-α、IL-4或抗CD40-Ab等刺激下表现出与HC APC不同的反应，这些反应可能在AD患者辅助T细胞向Th2细胞的极化过程中起作用。

Atopic dermatitis (AD) is characterized by the presence of Th2 type cells in the skin infiltration as well as in the peripheral blood, although a predominant infiltration of interferon-γ (IFN-γ)-producing cells is also reported in the chronic skin lesions of AD. Recently it has become clear that the development of Th1 or Th2 is strongly influenced by factors produced by the antigen presenting cells (APCs). To clarify whether APCs from AD patients play a favorable role in the differentiation of Th2 cells, we compared the production of cytokines and the expression of co-stimulatory molecules by monocytes (MOs) and monocyte-derived DCs (MoDCs) after stimulations with various reagents between 13 AD patients and 13 age-matched healthy controls. We examined their production of IL-1β, IL-10, IL-12p40, and IL-12p70, and their expression of CD23, CD40, CD54, CD80, CD83, CD86 and HLA-DR. We stimulated them with superantigens, LPS, agonistic anti-CD40 antibody, phytohemagglutinins (PHA), IL-1β/TNF-α, IL-4, or IFN-γ. The following results were obtained : 1) IL-10 production was significantly enhanced in AD MOs after LPS stimulation. In contrast, IL-12p40 production was significantly lower in AD MOs than in HC MOs after a variety of stimulations. 2) IL-12p40 was also significantly lower in AD MoDCs after LPS stimulation. 3) The induction of CD23 with IL-4 was significantly higher in AD MOs. And finally, 4) AD MoDCs augmented the expression of CD83, CD86, and HLA-DR less significantly than HC MoDCs after anti-CD40 Ab stimulation.These data indicate that AD APCs show some responses different from those observed in HC APCs after several stimulations, such as LPS, IL-1β/TNF-α, IL-4, or anti-CD40 Ab, and that these responses might play a role in the polarizing process of helper T cells into Th2 cells as recognized in AD patients.