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

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 ROR?(+) ILC3s into wounded dermis; ROR?(+) ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for ROR?(+) ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNF? and the ILC3 recruitment chemokines CCL20 and CXCL13. TNF?, 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.

SUBMITTER: Li Z 

PROVIDER: S-EPMC4844683 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature