A wave of monocytes is recruited to replenish the long-term Langerhans cell network after immune injury
A wave of monocytes is recruited to replenish the long-term Langerhans cell network after immune injury
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DOI：
10.1126/sciimmunol.aax8704
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发表时间：
2019-08-01
影响因子：
24.8
通讯作者：
Bennett, Clare L.
中科院分区：
文献类型：
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作者：
Ferrer, Ivana R.;West, Heather C.;Bennett, Clare L.
胚胎来源的朗格汉斯细胞(ELCs)在封闭的表皮内维持着密集的群体，循环细胞没有贡献。当这一网络被短暂的紫外线照射所干扰时，短期LC由最初的单核细胞波暂时重建，但被认为被具有未确定LC前体的更永久的再繁殖所取代。然而，这一过程在多大程度上与破坏LC群体完整性的免疫病理过程相关尚不清楚。在异基因造血干细胞移植的模型中，同种异体反应性T细胞直接以ELCs为靶点，我们询问是否以及如何最终恢复原始的LC网络。我们发现供者单核细胞，而不是树突状细胞，是长期LCS的前驱细胞。ELCs的破坏导致一波单核细胞的募集，这些单核细胞植入表皮，并通过转录上不同的EpCAM(+)前体经历一系列的分化途径。单核细胞来源的LCs获得自我更新的能力，并且在表皮中的增殖与稳定状态的ELCs相匹配。然而，我们发现了表皮单核细胞分化和存活的瓶颈，再加上成熟LC更新速度慢，限制了网络的修复。此外，LC网络的补充导致细胞结构性地进入表皮隔室。因此，免疫损伤触发了用于维持其他部位组织驻留巨噬细胞的机制的功能适应，但这一过程在皮肤中效率极低。
A dense population of embryo-derived Langerhans cells (eLCs) is maintained within the sealed epidermis without contribution from circulating cells. When this network is perturbed by transient exposure to ultraviolet light, short-term LCs are temporarily reconstituted from an initial wave of monocytes but thought to be superseded by more permanent repopulation with undefined LC precursors. However, the extent to which this process is relevant to immunopathological processes that damage LC population integrity is not known. Using a model of allogeneic hematopoietic stem cell transplantation, where alloreactive T cells directly target eLCs, we have asked whether and how the original LC network is ultimately restored. We find that donor monocytes, but not dendritic cells, are the precursors of long-term LCs in this context. Destruction of eLCs leads to recruitment of a wave of monocytes that engraft in the epidermis and undergo a sequential pathway of differentiation via transcriptionally distinct EpCAM(+) precursors. Monocyte-derived LCs acquire the capacity of self-renewal, and proliferation in the epidermis matched that of steady-state eLCs. However, we identified a bottleneck in the differentiation and survival of epidermal monocytes, which, together with the slow rate of renewal of mature LCs, limits repair of the network. Furthermore, replenishment of the LC network leads to constitutive entry of cells into the epidermal compartment. Thus, immune injury triggers functional adaptation of mechanisms used to maintain tissue-resident macrophages at other sites, but this process is highly inefficient in the skin.