Epidermal Notch1 recruits RORγ + group 3 innate lymphoid cells to orchestrate normal skin repair
Nature Communications , Volume 7
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.
|Department of Hematology
Li, Z., Hodgkinson, T., Gothard, E. J., Boroumand, S., Lamb, R., Cummins, I., … Ambler, C. A. (2016). Epidermal Notch1 recruits RORγ + group 3 innate lymphoid cells to orchestrate normal skin repair. Nature Communications, 7. doi:10.1038/ncomms11394