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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.

Original publication

DOI

10.1038/ncomms11394

Type

Journal article

Journal

Nat commun

Publication Date

21/04/2016

Volume

7

Keywords

Animals, Cell Movement, Chemokine CCL20, Chemokine CXCL13, Epidermis, Female, Gene Expression Regulation, Immunity, Innate, Interleukin-17, Lymphocyte Subsets, Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Nuclear Receptor Subfamily 1, Group F, Member 3, Receptor, Notch1, Signal Transduction, Tumor Necrosis Factor-alpha, Wound Healing, Wounds, Penetrating