Epidermal Notch1 recruits ROR gamma(+) group 3 innate lymphoid cells to orchestrate normal skin repair

Z Li, T Hodgkinson, EJ Gothard, S Boroumand, R Lamb, I Cummins, P Narang, A Sawtell, J Coles, G Leonov, A Reboldi, CD Buckley, Tom Cupedo, C Siebel, A Bayat, MC Coles, CA Ambler

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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 RORg gamma+ ILC3s into wounded dermis; ROR gamma+ ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for ROR gamma+ ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNF alpha and the ILC3 recruitment chemokines CCL20 and CXCL13. TNF alpha, 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 languageUndefined/Unknown
JournalNature Communications
Publication statusPublished - 2016

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