Transglutaminase 3 Promotes Skin Inflammation in Atopic Dermatitis by Activating Monocyte-Derived Dendritic Cells via DC-SIGN.
Transglutaminase 3 Promotes Skin Inflammation in Atopic Dermatitis by Activating Monocyte-Derived Dendritic Cells via DC-SIGN.
复制标题
转谷氨酰胺酶 3 通过 DC-SIGN 激活单核细胞衍生的树突细胞，促进特应性皮炎的皮肤炎症。
DOI：
10.1016/j.jid.2019.07.703
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发表时间：
2019
影响因子：
6.5
通讯作者：
Yao Xu
中科院分区：
文献类型：
--
作者：
Su Huichun;Luo Yang;Sun Jing;Liu Xiaochun;Ling Shiqi;Xu Beilei;Zhang Yu;Liu Jun;Li Wei;Wang Baoxi;Yao Xu
特应性皮炎（AD）通常伴随着对外来过敏原和自身过敏原的IgE水平升高。伴有自身过敏的AD患者病情更严重，治疗难度更大，自身反应性IgE可能是AD发病的一个因素。然而，免疫系统如何识别自身过敏原以及随后诱导的免疫反应在很大程度上仍然未知。我们发现AD患者血清中抗转谷氨酰胺酶3 （TGase3）的IgE水平明显高于健康人群，且与疾病严重程度呈正相关。与对照组相比，AD患者病变皮肤中TGase3的表达明显增加，Th2细胞因子和/或过敏原促进了TGase3在角质形成细胞中的表达。TGase3通过树突状细胞特异性icam -3非整合素（DC-SIGN）结合单核细胞衍生的树突状细胞（MoDCs），导致MoDCs中IL-6的产生和NF-κB信号通路的激活；tgase3处理的MoDCs促进Th1极化。此外，当TGase3被抑制时，mc903诱导的AD小鼠模型的皮肤炎症减轻。综上所述，TGase3在AD中是一种自身过敏原，并积极参与皮肤炎症反应；靶向tgase3可能是治疗AD的一种治疗策略。
Atopic dermatitis (AD) is often concomitant with increased levels of IgE against not only foreign allergens but also autoallergens. AD patients with autoallergy are likely to be more severe and difficult to treat, and self-reactive IgE might be a contributing factor in the pathogenesis of AD. However, how autoallergens are recognized by the immune system and what immune responses are induced subsequently remain largely unknown. We found that the serum level of IgE against transglutaminase 3 (TGase3) was significantly higher in AD patients than in healthy individuals and was positively correlated with disease severity. The expression of TGase3 in the lesional skin of AD patients was markedly increased compared with that of the controls, and Th2 cytokines and/or allergen promoted the expression of TGase3 in keratinocytes. TGase3 bond monocytes-derived dendritic cells (MoDCs) via dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), which resulted in the production of IL-6 and activation of the NF-κB signaling pathway in MoDCs; and TGase3-treated MoDCs facilitated Th1 polarization. Moreover, skin inflammation in the mouse model of MC903-induced AD was attenuated when TGase3 was inhibited. In conclusion, TGase3 was revealed as an autoallergen in AD and actively involved in skin inflammation; TGase3-targeting might be a therapeutic strategy for the treatment of AD.