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Loss of T cell tolerance in the skin following immunopathology is linked to failed restoration of the dermal niche by recruited macrophages



Bennett, Clare;

(2022)

Loss of T cell tolerance in the skin following immunopathology is linked to failed restoration of the dermal niche by recruited macrophages.

Cell Reports
, 39
(7)


, Article 110819. 10.1016/j.celrep.2022.110819.

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    Abstract

    T cell pathology in the skin leads to monocyte influx, but we have little understanding of the fate of recruited cells within the diseased niche, or the long-term impact on cutaneous immune homeostasis. By combining a murine model of acute graft-versus-host disease (aGVHD) with analysis of patient samples, we demonstrate that pathology initiates dermis-specific macrophage differentiation and show that aGVHD-primed macrophages continue to dominate the dermal compartment at the relative expense of quiescent MHCIIint cells. Exposure of the altered dermal niche to topical haptens after disease resolution results in hyper-activation of regulatory T cells (Treg), but local breakdown in tolerance. Disease-imprinted macrophages express increased IL-1β and are predicted to elicit altered TNF superfamily interactions with cutaneous Treg, and we demonstrate the direct loss of T cell regulation within the resolved skin. Thus, T cell pathology leaves an immunological scar in the skin marked by failure to re-set immune homeostasis.

    Type: Article

    Title: Loss of T cell tolerance in the skin following immunopathology is linked to failed restoration of the dermal niche by recruited macrophages
    Open access status: An open access version is available from UCL Discovery
    DOI: 10.1016/j.celrep.2022.110819
    Publisher version: https://doi.org/10.1016/j.celrep.2022.110819
    Language: English
    Additional information: © 2022 The Authors. Published under a Creative Commons license (https://creativecommons.org/licenses/by/4.0/).
    Keywords: skin, monocytes, macrophages, dermis, graft-versus-host disease, disease niche, regulatory T cells, tolerance, contact hypersensitivity
    UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
    UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
    UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
    UCL
    UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
    URI: https://discovery.ucl.ac.uk/id/eprint/10148694

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