Li, Zhi orcid.org/0000-0002-0583-1116, Hodgkinson, Tom, Gothard, Elizabeth Jane et al. (13 more authors) (2016) Epidermal Notch1 recruits RORγ+ group 3 innate lymphoid cells to orchestrate normal skin repair. Nature Communications. 11394. ISSN 2041-1723
Abstract
Notch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epidermal Notch induces recruitment of immune cell subsets including RORγ + ILC3s into wounded dermis; RORγ + ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for RORγ + ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNFα and the ILC3 recruitment chemokines CCL20 and CXCL13. TNFα, as a Notch1 effector, directs ILC3 localization and rates of wound healing. Altogether these findings suggest that Notch is a key stress/injury signal in skin epithelium driving innate immune cell recruitment and normal skin tissue repair.
Metadata
Authors/Creators: |
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Keywords: | Animals, Cell Movement/immunology, Chemokine CCL20/genetics, Chemokine CXCL13/genetics, Epidermis/immunology, Female, Gene Expression Regulation, Immunity, Innate, Interleukin-17/genetics, Lymphocyte Subsets/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Nuclear Receptor Subfamily 1, Group F, Member 3/deficiency, Receptor, Notch1/genetics, Signal Transduction/immunology, Tumor Necrosis Factor-alpha/genetics, Wound Healing/genetics, Wounds, Penetrating/genetics |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Mathematics (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 06 May 2016 14:20 |
Last Modified: | 04 Feb 2024 00:41 |
Published Version: | https://doi.org/10.1038/ncomms11394 |
Status: | Published |
Refereed: | Yes |
Identification Number: | https://doi.org/10.1038/ncomms11394 |
Related URLs: |