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to ultraviolet light, short-term LCs are temporarily reconstituted from an initial wave of monocytes but thought to be superseded by more permanent repopulation with undefined LC precursors.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.

密闭的表皮内保持着密集的胚胎来源的朗格汉斯细胞（eLC），而不受循环细胞的影响。当该网络受到短暂暴露于紫外线的干扰时，短期LC会从单核细胞的初始波中暂时重建，但被不确定的LC前体的更多永久性种群所取代。但是，该过程与损害LC群体完整性的免疫病理学过程相关的程度尚不清楚。使用同种异体造血干细胞移植模型，其中同种异体反应性T细胞直接靶向eLC，我们询问了是否以及如何最终恢复了原始LC网络。我们发现，在这种情况下，供体单核细胞而非树突状细胞是长期LC的前体。⁺前体。单核细胞衍生的LC具有自我更新的能力，表皮中的增殖与稳态eLC的增殖相匹配。但是，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的更新速度缓慢，限制了网络的修复。此外，LC网络的补充导致细胞组成性进入表皮区室。因此，免疫损伤触发了用于在其他部位维持组织驻留巨噬细胞的机制的功能适应，但是该过程在皮肤中效率极低。