CCR7-independent transport of skin antigens occurs in the dermis
CCR7-independent transport of skin antigens occurs in the dermis
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皮肤抗原的 CCR7 独立运输发生在真皮中
DOI：
10.1002/eji.201142114
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
S.I.
中科院分区：
文献类型：
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作者：
Yoshino;M.;Okuyama;K.;Murata;A.;Tomura;M.;and Hayashi;S.I.
在稳态条件下，皮肤dc迁移到运输自身抗原（self - Ags）的区域ln。自体Ags的转运被认为是维持外周耐受性的关键。虽然趋化因子受体CCR7能有效诱导皮肤dc向区域LNs迁移，但CCR7−/−（CCR7‐KO）小鼠并未表现出皮肤自身免疫性疾病。为了解决这种不一致，我们研究了ccr7‐KOepidermis‐或真皮‐色素沉着转基因（Tg）小鼠，其中皮肤自身Ags的运输可通过黑色素颗粒（mg）追踪。在缺乏CCR7的条件下，表皮mg向局部LNs的转运在7周龄时受损。然而，当mg积聚在真皮层时，表皮mg可以被运输。Ccr7 - KO -真皮色素Tg小鼠证实了真皮中存在不依赖Ccr7的转运。与WT -真皮着色Tg小鼠相比，ccr7 - KO -真皮着色Tg小鼠的皮肤区域LNs中，转运黑色素的数量和CD11c+细胞的数量均约为WT水平的40%，而CD205+或CD207+细胞的数量减少至约10%。细胞分选强调了CD11c+细胞参与CCR7非依赖性转运。在这里，我们发现不依赖CCR7的皮肤自身Ags转运发生在真皮层。该系统可能有助于自身Ags的连续运输，并维持外周耐受性。
Under homeostatic conditions, skin DCs migrate to regional LNs transporting self‐antigens (self‐Ags). The transport of self‐Ags is considered to be critical for maintaining peripheral tolerance. Although the chemokine receptor CCR7 potently induces the migration of skin DCs to regional LNs,Ccr7−/−(Ccr7‐KO) mice do not show skin auto‐immune diseases. To resolve this inconsistency, we examinedCcr7‐KOepidermis‐ or dermis‐hyperpigmented transgenic (Tg) mice, in which the transport of skin self‐Ags is traceable by melanin granules (MGs). Under CCR7‐deficient conditions, the transport of epidermal MGs to regional LNs was impaired at 7 weeks of age. However, epidermal MGs could be transported when they had accumulated in the dermis.Ccr7‐KO‐dermis‐pigmented Tg mice confirmed the presence of CCR7‐independent transport from the dermis. Compared with WT‐dermis‐pigmented Tg mice, the amount of transported melanin and number of MG‐laden CD11c+cells were both approximately 40% of the WT levels, while the number of MG‐laden CD205+or CD207+cells decreased to about 10% in skin regional LNs ofCcr7‐KO‐dermis‐pigmented Tg mice. Cell sorting highlighted the involvement of CD11c+cells in the CCR7‐independent transport. Here, we show that CCR7‐independent transport of skin self‐Ags occurs in the dermis. This system might contribute to the continuous transport of self‐Ags, and maintain peripheral tolerance.