In Situ Mapping of Innate Lymphoid Cells in Human Skin: Evidence for Remarkable Differences between Normal and Inflamed Skin
In Situ Mapping of Innate Lymphoid Cells in Human Skin: Evidence for Remarkable Differences between Normal and Inflamed Skin
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DOI：
10.1016/j.jid.2016.07.017
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发表时间：
2016-12-01
影响因子：
6.5
通讯作者：
Stingl, Georg
中科院分区：
文献类型：
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作者：
Brueggen, Marie-Charlotte;Bauer, Wolfgang M.;Stingl, Georg
虽然先天性淋巴样细胞（ILC）最近也在皮肤中被发现，但它们在该器官中的作用仍然知之甚少。在这项研究中，我们的目的是开发一种技术，以评估ILC在原位，并确定其在人体皮肤的地形分布。我们收集了特应性皮炎和银屑病患者（均为n = 13）和健康对照组的正常人皮肤的病变皮肤活检。在建立免疫荧光ILC原位染色后，我们开发了一种分析方法（门控结合手动验证）来可靠地识别ILC。通过自动计算ILC与皮肤的不同细胞/结构元素之间的距离来获得地形图。正常人皮肤中ILC数量极少（大多数为ILC 1和AHR（+）ILC 3），而特应性皮炎和银屑病皮肤中则有清晰可见的ILC亚群浸润。我们观察到特应性皮炎皮肤不仅含有ILC 2，而且还含有显著的AHR（+）ILC 3群体。相反，我们在银屑病皮肤中发现了几乎相同比例的ILC 1和RORC（+）ILC 3。距离计算显示ILC位于表皮附近，并靠近T淋巴细胞。ILC原位定位将提供关于它们在正常和患病皮肤中可能的通信伙伴的有价值的信息，并形成适当的机制研究的基础。
Although innate lymphoid cells (ILCs) have recently been identified also in skin, their role in this organ remains poorly understood. In this study, we aimed at developing a technique to assess ILCs in situ and to determine their topographical distribution in human skin. We collected lesional skin biopsies from patients with atopic dermatitis and psoriasis (both n = 13) and normal human skin from healthy controls. After establishing immunofluorescence ILC in situ stainings, we developed an analysis approach (gating combined with manual validation) to reliably identify ILCs. Topographical mapping was obtained by automated calculations of the distances between ILCs and different cellular/structural elements of the skin. Whereas normal human skin harbored a very scarce ILC population (mostly ILC1s and AHR(+)ILC3s), atopic dermatitis and psoriasis skin was infiltrated by clearly visible ILC subsets. We observed atopic dermatitis skin to contain not only ILC2s but also a prominent AHR(+)ILC3 population. Conversely, we encountered almost equal proportions of ILC1s and RORC(+)ILC3s in psoriasis skin. Distance calculations revealed ILCs to reside near the epidermis and in close proximity to T lymphocytes. ILC mapping in situ will provide valuable information about their likely communication partners in normal and diseased skin and forms the basis for the appropriate mechanistic studies.