Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus
Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus
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DOI：
10.1016/j.immuni.2006.02.006
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发表时间：
2006-03-01
期刊：
影响因子：
32.4
通讯作者：
Leung, DYM
中科院分区：
文献类型：
--
作者：
Howell, MD;Gallo, RL;Leung, DYM
特应性皮炎（AD）与牛痘性湿疹（EV）有关，这是一种接种牛痘病毒（VV）后发生的播散性病毒性皮肤感染。本研究检测了AD皮肤是否可以控制VV复制，以及IL-4和IL-13在调节人cathelicidin LL-37（一种杀死VV的抗菌肽）中的作用。与正常或银屑病皮肤相比，AD皮肤表现出VV复制增加和LL-37表达降低。IL-4/IL-13增强VV复制，同时下调VV刺激的角质形成细胞中的LL-37。中和AD皮肤中的IL-4/IL-13增强LL-37并抑制VV复制。Cathelicidins通过toll样受体-3诱导，并通过STAT-6被IL-4/IL-13抑制。cathelicidin缺陷小鼠的皮肤表现出控制VV复制的能力降低。外源性LL-37控制牛痘病毒在感染的角质形成细胞和AD皮肤外植体中的复制。目前的研究表明，Th 2细胞因子通过以STAT-6依赖的方式破坏针对VV的先天免疫应答来增强AD皮肤中的VV复制。
Atopic dermatitis (AD) is associated with eczema vaccinatum (EV), a disseminated viral skin infection that follows inoculation with vaccinia virus (VV). This study examined whether AD skin can control VV replication, and the role of IL-4 and IL-13 in modulating the human cathelicidin LL-37, an antimicrobial peptide that kills VV. AD skin exhibited increased VV replication and decreased LL-37 expression compared to normal or psoriasis skin. IL-4/IL-13 enhanced VV replication while downregulating LL-37 in VV-stimulated keratinocytes. Neutralizing IL-4/IL-13 in AD skin augmented LL-37 and inhibited VV replication. Cathelicidins were induced via toll-like receptor-3 and were inhibited by IL-4/IL-13 through STAT-6. Skin from cathelicidin-deficient mice exhibited reduced ability to control VV replication. Exogenous LL-37 controlled vaccinia viral replication in infected keratinocytes and AD skin explants. The current study demonstrates that Th2 cytokines enhance VV replication in AD skin by subverting the innate immune response against VV in a STAT-6-dependent manner.