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特应性皮炎成人中由Toll样受体2和7/8调节的调节性髓样树突状细胞和循环炎性表皮树突状细胞样细胞的证据。

Evidence of regulatory myeloid dendritic cells and circulating inflammatory epidermal dendritic cells-like modulated by Toll-like receptors 2 and 7/8 in adults with atopic dermatitis.

作者信息

Dos Santos Vanessa G, Orfali Raquel L, de Oliveira Titz Tiago, da Silva Duarte Alberto J, Sato Maria N, Aoki Valeria

机构信息

Department of Dermatology, Laboratory of Dermatology and Immunodeficiency (LIM-56), University of Sao Paulo School of Medicine, Sao Paulo-SP, Brazil.

出版信息

Int J Dermatol. 2017 Jun;56(6):630-635. doi: 10.1111/ijd.13537. Epub 2017 Jan 12.

Abstract

BACKGROUD

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and xerosis. Dendritic cells (DC) play an essential role in tissue inflammation in atopic dermatitis (AD) skin, especially the inflammatory epidermal dendritic cells (IDEC), a particular subset of myeloid dendritic cells (mDC). The aim of the present study was to assess the phenotype and function of mDC and circulating IDEC-like in peripheral blood mononuclear cells (PBMC) of adults with AD.

METHODS

We selected 21 AD patients and 21 non-AD controls, age and gender matched. Expressions of FcεRI, CD36, TNF, IFN- γ, and IL-10 in mDC were analyzed by flow cytometry under various stimuli, such as staphylococcal enterotoxin B (SEB), TLR2 (Pam3CSK4), TLR4 (LPS), and TLR7/8 (CL097) agonists.

RESULTS

The most prominent findings in AD patients were: (i) enhanced frequency of IL-10 under TLR4 (LPS), and decreased frequency of IFN-γ and TNF under TLR2 (Pam3CSK4) and 7/8 (CL097) stimulation in classic mDC; (ii) elevation of circulating IDEC-like frequency with TLR2 (Pam3CSK4) stimuli, augmented frequency of IFN-γ in nonstimulated condition, and of IL-10 under TLR7/8 (CL097) stimuli in IDEC-like population.

CONCLUSIONS

In AD individuals, classic mDC showed an immunomodulatory profile, favoring tolerance in a combined action with IDEC-like, and inducing Th1 polarization. Our findings indicate a potential role of IDEC-like in the maintenance of inflammation in atopic dermatitis patients; moreover, IDEC-like may exert a regulatory impact on T cells of AD individuals through IL-10, often induced by agonist mimicking single stranded RNA virus.

摘要

背景

特应性皮炎(AD)是一种慢性炎症性皮肤病,其特征为剧烈瘙痒和皮肤干燥。树突状细胞(DC)在特应性皮炎(AD)皮肤的组织炎症中起重要作用,尤其是炎症性表皮树突状细胞(IDEC),它是髓样树突状细胞(mDC)的一个特殊亚群。本研究的目的是评估成年AD患者外周血单个核细胞(PBMC)中mDC和循环中类似IDEC细胞的表型及功能。

方法

我们选取了21例AD患者和21例年龄、性别匹配的非AD对照。在各种刺激下,如葡萄球菌肠毒素B(SEB)、Toll样受体2(Pam3CSK4)、Toll样受体4(LPS)和Toll样受体7/8(CL097)激动剂,通过流式细胞术分析mDC中FcεRI、CD36、肿瘤坏死因子(TNF)、干扰素-γ(IFN-γ)和白细胞介素-10(IL-10)的表达。

结果

AD患者最显著的发现为:(i)在经典mDC中,Toll样受体4(LPS)刺激下IL-10频率增加,而Toll样受体2(Pam3CSK4)和7/8(CL097)刺激下IFN-γ和TNF频率降低;(ii)在类似IDEC细胞群体中,Toll样受体2(Pam3CSK4)刺激下循环中类似IDEC细胞频率升高,未刺激条件下IFN-γ频率增加,Toll样受体7/8(CL097)刺激下IL-10频率增加。

结论

在AD个体中,经典mDC表现出免疫调节特征,与类似IDEC细胞共同作用有利于免疫耐受,并诱导Th1极化。我们的研究结果表明类似IDEC细胞在AD患者炎症维持中可能发挥作用;此外,类似IDEC细胞可能通过IL-10对AD个体的T细胞产生调节作用,IL-10通常由模拟单链RNA病毒的激动剂诱导产生。

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