Compartmental imbalance and aberrant immune function of blood CD123+ (plasmacytoid) and CD11c+ (myeloid) dendritic cells in atopic dermatitis

Compartmental imbalance and aberrant immune function of blood CD123+ (plasmacytoid) and CD11c+ (myeloid) dendritic cells in atopic dermatitis
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DOI:
10.4049/jimmunol.174.4.2396
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发表时间:
2005-02-15
影响因子:
4.4
通讯作者:
Takigawa, M
Takigawa, M
中科院分区:
医学2区
文献类型:
--
作者:
Hashizume, H;Horibe, T;Takigawa, M

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特应性皮炎 (AD) 是一种瘙痒性、慢性复发性皮肤病,其中 Th2 细胞在皮肤和皮外免疫反应中发挥着至关重要的作用。在人类中,CD11c(+)-CD123(-) 骨髓树突状细胞 (mDC) 和 CD11c(-)CD123(+) 浆细胞样 DC (pDC) 协调先天性和获得性免疫的决策过程。据报道,这些血液树突状细胞 (DC) 亚群的数量和功能反映了宿主的免疫状态,因此我们研究了 DC 亚群在 AD 发病机制中的参与。与正常人和银屑病患者(Th1疾病模型组)相比,AD患者外周血中DC数量增加,mDC:pDC比率较低,pDC数量超过mDC。 mDC:pDC比率与总血清IgE水平、产生IFN-γ的血细胞与产生IL-4的血细胞的比率以及疾病严重程度相关。体外用特应性DC同种异体刺激初始CD4(+)细胞表明pDC诱导Th1的能力优于或与mDC相当。在皮肤病变中,pDC浸润与表达外周神经地址素的血管密切相关。因此,血液DC亚群的区室失衡和异常的免疫功能可能会偏离Th1/Th2分化,从而诱发AD的长期过敏反应。
Atopic dermatitis (AD) is a pruritic, chronically relapsing skin disease in which Th2 cells play a crucial role in cutaneous and extracutaneous immune reactions. In humans, CD11c(+)-CD123(-) myeloid dendritic cells (mDC) and CD11c(-)CD123(+) plasmacytoid DC (pDC) orchestrate the decision-making process in innate and acquired immunity. Since the number and function of these blood dendritic cell (DC) subsets reportedly reflect the host immune status, we studied the involvement of the DC subsets in the pathogenesis of AD. Patients with AD had an increased DC number and a low mDC:pDC ratio with pDC outnumbering mDC in the peripheral blood compared with normal subjects and psoriasis patients (a Th1 disease model group). The mDC:pDC ratio was correlated with the total serum IgE level, the ratio of IFN-gamma-producing blood cells: IL-4-producing blood cells, and the disease severity. In vitro allogeneic stimulation of naive CD4(+) cells with atopic DC showed that the ability of pDC for Th1 induction was superior or comparable to that of mDC. In skin lesions, pDC infiltration was in close association with blood vessels expressing peripheral neural addressins. Therefore, compartmental imbalance and aberrant immune function of the blood DC subsets may deviate the Th1/Th2 differentiation and thus induce protracted allergic responses in AD.