Tissue-resident macrophages can be generated de novo in adult human skin from resident progenitor cells during substance P-mediated neurogenic inflammation ex vivo
Tissue-resident macrophages can be generated de novo in adult human skin from resident progenitor cells during substance P-mediated neurogenic inflammation ex vivo
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DOI：
10.1371/journal.pone.0227817
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发表时间：
2020-01-23
期刊：
影响因子：
3.7
通讯作者：
Paus, Ralf
中科院分区：
文献类型：
--
作者：
Gherardini, Jennifer;Uchida, Youhei;Paus, Ralf
除了单核细胞（MO）衍生的巨噬细胞（MAC），自我更新的组织驻留巨噬细胞（trMAC）维持小鼠皮肤中的皮内MAC池。在这里，我们问是否同样的现象发生在人体皮肤使用器官培养，全层皮肤脱离血液循环和骨髓。模拟神经源性皮肤炎症，用神经肽P物质（SP）离体刺激皮肤，可显著增加乳头状真皮中CD 68（+）MAC的数量，而不改变皮内MAC的增殖或凋亡。由于在非灌注的真皮血管系统中检测不到管腔内的CD 14（+）MO，因此新的MAC一定是从人皮肤中的固有皮内祖细胞分化而来的。有趣的是，CD 68（+）MAC经常与同时表达造血干细胞标志物CD 34和SP受体（神经激肽-1受体[NK 1 R]）的细胞直接细胞接触。在SP处理的皮肤样品中，这些细胞-细胞接触和CD 34（+）细胞增殖上调。总的来说，我们的研究提供了第一个证据，即在正常成人皮肤中确实存在居民MAC祖细胞，成熟MAC可以在组织内迅速分化。这些NK 1 R（+）trMAC祖细胞对关键的应激相关神经炎性刺激迅速做出反应，表明这可能满足了创伤/应激条件下增加的局部MAC需求。
Besides monocyte (MO)-derived macrophages (MACs), self-renewing tissue-resident macrophages (trMACs) maintain the intracutaneous MAC pool in murine skin. Here, we have asked whether the same phenomenon occurs in human skin using organ-cultured, full-thickness skin detached from blood circulation and bone marrow. Skin stimulation ex vivo with the neuropeptide substance P (SP), mimicking neurogenic skin inflammation, significantly increased the number of CD68(+) MACs in the papillary dermis without altering intracutaneous MAC proliferation or apoptosis. Since intraluminal CD14(+) MOs were undetectable in the non-perfused dermal vasculature, new MACs must have differentiated from resident intracutaneous progenitor cells in human skin. Interestingly, CD68(+) MACs were often seen in direct cell-cell-contact with cells expressing both, the hematopoietic stem cell marker CD34 and SP receptor (neurokinin-1 receptor [NK1R]). These cell-cell contacts and CD34(+) cell proliferation were up-regulated in SP-treated skin samples. Collectively, our study provides the first evidence that resident MAC progenitors, from which mature MACs can rapidly differentiate within the tissue, do exist in normal adult human skin. That these NK1R(+) trMAC-progenitor cells quickly respond to a key stress-associated neuroinflammatory stimulus suggests that this may satisfy increased local MAC demand under conditions of wounding/stress.