Ccr6 Is Dispensable for the Development of Skin Lesions Induced by Imiquimod despite its Effect on Epidermal Homing of IL-22-Producing Cells
Ccr6 Is Dispensable for the Development of Skin Lesions Induced by Imiquimod despite its Effect on Epidermal Homing of IL-22-Producing Cells
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DOI：
10.1016/j.jid.2016.12.023
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发表时间：
2017-05-01
影响因子：
6.5
通讯作者：
Dumoutier, Laure
中科院分区：
文献类型：
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作者：
Cochez, Perrine M.;Michiels, Camille;Dumoutier, Laure
趋化因子受体Ccr6的表达是大多数IL-22产生细胞共有的，Ccr6缺陷小鼠在皮内注射IL-23后IL-22产生减少和皮肤炎症。为了确定这一观察结果是否可以扩展到另一种牛皮癣模型，我们将咪喹莫特应用于ccr6缺陷小鼠。尽管这些小鼠由于γ δ T细胞募集不足导致表皮IL-22的产生减少，但它们对银屑病病变没有保护作用。当用IL-1 α /IL-2/IL-23刺激未处理小鼠的原代表皮或真皮组织培养细胞时，我们观察到Ccr6对表皮而非真皮培养的il - 22表达至关重要。利用Ccr6- lacz敲入小鼠，我们发现Ccr6对于Ccr6阳性细胞的归巢是必需的，可能是γ δ t细胞亚群，它代表了表皮中IL-22的主要潜在来源。在Rag1（-/-）表皮和真皮原代培养中也观察到类似的结果，其中表达Ccr6的先天淋巴样细胞亚群是IL-22的主要潜在来源。综上所述，我们的数据表明，尽管Ccr6对产生il -22的细胞的表皮归巢有影响，但它在咪喹莫特诱导的皮肤病变的发展中并不是必需的。
Expression of the chemokine receptor Ccr6 is shared by most IL-22-producing cells, and Ccr6-deficient mice showed decreased IL-22 production and skin inflammation upon IL-23 intradermal injections. To determine whether this observation might be extended to another psoriasis model, we applied imiquimod on Ccr6-deficient mice. Although epidermal IL-22 production was decreased because of a deficient recruitment of gamma delta T cells in these mice, they were not protected against psoriatic lesions. When primary epidermis or dermis tissue culture cells from nontreated mice were stimulated ex vivo with IL-1 alpha/IL-2/IL-23, we observed that Ccr6 is crucial for Il22 expression from epidermal but not dermal cultures. Taking advantage of Ccr6-LacZ-knock-in mice, we showed that Ccr6 is necessary for the homing of Ccr6-positive cells, probably a gamma delta T-cell subset, which represents the main potential IL-22 source in the epidermis. Similar results were observed in Rag1(-/-) epidermis and dermis primary cultures, in which a subset of innate lymphoid cells expressing Ccr6 represents the main potential source of IL-22. Taken together, our data show that Ccr6 is not required for the development of skin lesions induced by imiquimod despite its effect on epidermal homing of IL-22-producing cells.