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

特应性皮炎或银屑病患者树突状细胞功能改变的分析

• 批准号: 12670803
• 负责人: AIBA Setsuya
• 金额: $ 2.05万
• 依托单位: Tohoku University Graduate School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670803/
• 关键词: Atopic dermatitis; Psoriasis; dendritic cells; cytokine; IL-10; CD86; luekotriene; IL-12

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.

特应性皮炎（AD）的特征在于皮肤浸润以及外周血中存在Th 2型细胞，尽管在AD的慢性皮肤病变中也报道了产生干扰素-γ（IFN-γ）的细胞的主要浸润。最近已经清楚的是，Th 1或Th 2的发育受到抗原呈递细胞（APC）产生的因子的强烈影响。为了阐明AD患者的APC是否在Th 2细胞的分化中发挥有利的作用，我们比较了13名AD患者和13名年龄匹配的健康对照者在用各种试剂刺激后单核细胞（MO）和单核细胞衍生的DC（MoDC）的细胞因子产生和共刺激分子的表达。用超抗原、LPS、抗CD 40抗体、植物血凝素（PHA）、IL-1β/TNF-α、IL-4或IFN-γ刺激细胞，检测细胞产生IL-1β、IL-10、IL-12 p40和IL-12 p70，以及表达CD 23、CD 40、CD 54、CD 80、CD 83、CD 86和HLA-DR。结果表明：（1）脂多糖刺激后AD MO细胞产生IL-10的能力明显增强。相比之下，IL-12 p40的生产是显着较低的AD MOs比HC MOs后，各种刺激。2)LPS刺激后，AD MoDC中的IL-12 p40也显著降低。3)在AD MO中，IL-4对CD 23的诱导显著更高。4）抗CD 40抗体刺激后，AD MoDCs对CD 83、CD 86和HLA-DR表达的促进作用低于HC MoDCs，提示AD APCs对LPS、IL-1β/TNF-α、IL-4、抗CD 40抗体等多种刺激后的反应与HC APCs不同。并且这些反应可能在辅助性T细胞极化为AD患者中所识别的Th 2细胞的过程中起作用。

项目成果

Mollah, Z, Aiba, S., et al.: "Cord Blood CD34_+ Cells Differentiate into Dermal Dendritic Celss in Co-culture with Cutaneous Fibroblasts or Stromal Cells"Journal of Investigative Dermatology. 118(in press). (2002)

Mollah，Z，Aiba，S.等人：“脐带血CD34_细胞与皮肤成纤维细胞或基质细胞共培养时分化为真皮树突细胞”皮肤病学研究杂志。

Aiba,S: "Dermatofibroma with diffuse eosinophilic infiltrate"Am J Dermatopathol. 22. 281-284 (2000)

Aiba，S：“伴有弥漫性嗜酸性粒细胞浸润的皮肤纤维瘤”Am J Dermatopathol。

Iguchi, M, Aiba, S. et al.: "Human follicular papilla cells carry out nonadipose tissue production of leptin"Journal of Investigative Dermatology. 117. 1349-1356 (2001)

Iguchi, M, Aiba, S. 等人：“人类毛囊乳头细胞进行非脂肪组织瘦素的产生”《皮肤病学研究杂志》。

Aiba, S. et al: "Alteration in the production of IL-10 and IL-12 and aberrant expression of CD23, CD83, and C86 by monocytes or monocyte-derived dendritic cells from atopic dermatitis patients"Exp. Dermatol. (in press).

Aiba, S. 等人：“来自特应性皮炎患者的单核细胞或单核细胞衍生的树突细胞产生 IL-10 和 IL-12 的变化以及 CD23、CD83 和 C86 的异常表达”Exp。

Iguchi, M, Aiba, S., et al.: "Human follicular papilla cells carry out nonadipose tissue production of leptin"Journal of Investigative Dermatology. 117. 1349-1356 (2001)

Iguchi, M, Aiba, S. 等人：“人类毛囊乳头细胞进行非脂肪组织瘦素的产生”《皮肤病学研究杂志》。