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A wave of monocytes is recruited to replenish the long-term Langerhans cell network after immune injury

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Title: A wave of monocytes is recruited to replenish the long-term Langerhans cell network after immune injury
Authors: Ferrer, IR
West, HC
Henderson, S
Ushakov, DS
Sousa, PSE
Strid, J
Chakraverty, R
Yates, AJ
Bennett, CL
Item Type: Journal Article
Abstract: 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to ultraviolet light, short-term LCs are temporarily reconstituted from an initial wave of monocytes but thought to be superseded by more permanent repopulation with undefined LC precursors.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.
Issue Date: 23-Aug-2019
Date of Acceptance: 15-Jul-2019
URI: http://hdl.handle.net/10044/1/73672
DOI: https://dx.doi.org/10.1126/sciimmunol.aax8704
ISSN: 2470-9468
Publisher: American Association for the Advancement of Science
Start Page: 1
End Page: 14
Journal / Book Title: Science Immunology
Volume: 4
Issue: 38
Copyright Statement: © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
DERMAL DENDRITIC CELLS
CD8(+) T-CELLS
STEADY-STATE
DISTINCT
DEVELOP
SKIN
MACROPHAGES
EXPRESSION
MIGRATION
IL-34
Science & Technology
Life Sciences & Biomedicine
Immunology
DERMAL DENDRITIC CELLS
CD8(+) T-CELLS
STEADY-STATE
DISTINCT
DEVELOP
SKIN
MACROPHAGES
EXPRESSION
MIGRATION
IL-34
Publication Status: Published
Article Number: ARTN eaax8704
Online Publication Date: 2019-08-23
Appears in Collections:Department of Immunology and Inflammation