Tissue-resident macrophages can be generated de novo in adult human skin from resident progenitor cells during substance P-mediated neurogenic inflammation ex vivo

Autoři: Jennifer Gherardini aff001;  Youhei Uchida aff002;  Jonathan A. Hardman aff003;  Jérémy Chéret aff004;  Kimberly Mace aff005;  Marta Bertolini aff001;  Ralf Paus aff001
Působiště autorů: Monasterium Laboratory GmbH, Münster, Germany aff001;  Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan aff002;  Centre for Dermatology Research and NIHR Manchester Biomedical Research Centre University of Manchester, Manchester, United Kingdom aff003;  Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, United States of America aff004;  Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227817


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.

Klíčová slova:

Dermis – Epidermis – Image analysis – Mast cells – Quantitative analysis – Scanning electron microscopy – Skin – Stem cells


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