A single wave of monocytes is sufficient to replenish the long-term Langerhans cell network after immune injury
| Autor: | Andrew J. Yates, Clare L. Bennett, Stephen Henderson, Pedro Santos e Sousa, Heather C. West, Ronjon Chakraverty, Dmitry S. Ushakov, Jessica Strid, Ivana R. Ferrer |
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| Rok vydání: | 2019 |
| Předmět: |
education.field_of_study
Langerhans cell Epidermis (botany) Chemistry medicine.medical_treatment Compartment (ship) Population Context (language use) Hematopoietic stem cell transplantation Cell biology Immune system medicine.anatomical_structure medicine education Proto-oncogene tyrosine-protein kinase Src |
| DOI: | 10.1101/617514 |
| Popis: | Embryo-derived Langerhans cells (eLC) are maintained within the sealed epidermis without contribution from circulating cells. When the network is perturbed by transient exposure to ultra-violet light, short-term LC are temporarily reconstituted from an initial wave of monocytes, but thought to be superseded by more permanent repopulation with undefined LC precursors.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 mechanism is relevant to immune-pathological processes that damage LC population integrity is not known. Using a model of allogeneic hematopoietic stem cell transplantation, where allo-reactive T cells directly target eLC, we have asked if and how the original LC network is ultimately restored. We find that donor monocytes, but not dendritic cells, are the precursors of the long-term LC in this context. Destruction of eLC leads to recruitment of a single wave of monocytes which engraft in the epidermis and undergo a sequential pathway of differentiation via transcriptionally distinct EpCAM+precursors. Monocyte-derived LC acquire the capacity of self-renewal, and turn-over in the epidermis was remarkably similar to that of steady state eLC. However, we have identified a bottleneck in the differentiation and survival of epidermal monocytes, which together with the slow turn-over of mature LC 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.HighlightsImmune injury leads to recruitment of a single wave of monocytes to replace resident Langerhans cells (LC).DC lineage cells cannot become long-term replacement LC.The size of the re-emerging network is controlled by density-dependent division of mature LC.Immune injury and inefficient repopulation by monocyte-derived cells lead to a permanently altered LC niche. |
| Databáze: | OpenAIRE |
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