CCL17 transgenic mice show an enhanced Th2-type response to both allergic and non-allergic stimuli
CCL17 transgenic mice show an enhanced Th2-type response to both allergic and non-allergic stimuli
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DOI：
10.1002/eji.200535564
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发表时间：
2006-08-01
影响因子：
5.4
通讯作者：
Tamaki, Kunihiko
中科院分区：
文献类型：
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作者：
Tsunemi, Yuichiro;Saeki, Hidehisa;Tamaki, Kunihiko
CC 趋化因子配体 (CCL)17 与特应性皮炎 (AD) 的发病机制有关。为了研究角质形成细胞 (KC) 在炎症过程中产生的 CCL17 的作用，我们创建了转基因 (Tg) 小鼠，其中 CCL17 在 KC 中过度表达。在这些小鼠中，Th2 型接触性超敏反应 (CHS) 增强，而 Th1 型接触性超敏反应 (CHS) 受到抑制。 Tg 小鼠中浸润的 CC 趋化因子受体 (CCR)4(+) 细胞和肥大细胞数量增加。急性和慢性CHS中IL-4 mRNA水平较高，IFN-γ mRNA水平较低。 CHS 后观察到血清 IgE 水平较高。在躯干受到急性攻击的Tg小鼠中，PBMC中的CCR4(+)细胞数量增加。巴豆油慢性刺激引起皮炎和血清 IgE 水平升高。 Tg 小鼠在撕掉胶带后表现出耳朵肿胀加剧。 CCL17被认为可以通过将CCR4(+)细胞吸引到病变皮肤并产生Th2主导的条件来改变由敏化试剂和刺激性试剂引起的炎症。观察到类似 AD 的情况，例如肥大细胞数量增加和血清 IgE 水平升高。因此，CCL17可能通过调节过敏性和刺激性炎症参与AD等皮肤病的发病机制。
CC chemokine ligand (CCL)17 is implicated in the pathogenesis of atopic dermatitis (AD). To study the effect of CCL17 produced by keratinocytes (KC) during inflammation, we created transgenic (Tg) mice in which CCL17 is overexpressed in KC. Th2-type contact hypersensitivity (CHS) was enhanced and Th1-type CHS was suppressed in these mice. Increased numbers of CC chemokine receptor (CCR)4(+) cells and mast cells infiltrated in Tg mice. Levels of IL-4 mRNA were higher and those of IFN-gamma mRNA were lower in both acute and chronic CHS. Higher levels of serum IgE were observed after CHS. Numbers of CCR4(+) cells among PBMC were increased in Tg mice challenged acutely on the trunk. Chronic irritation with croton oil induced dermatitis and an elevation of serum IgE levels. Tg mice showed enhanced ear swelling after tape stripping. CCL17 was thought to modify the inflammation caused by sensitizing reagents as well as irritant reagents by attracting CCR4(+) cells into the lesional skin and creating a Th2-dominant condition. AD-like conditions such as increased number of mast cells and elevated levels of serum IgE were observed. Thus, CCL17 may participate in the pathogenesis of skin diseases such as AD by regulating both allergic and irritant inflammation.