Li, Z. and Hodgkinson, T. and Gothard, E.J. and Boroumand, S. and Lamb, R. and Cummins, I. and Narang, P. and Sawtell, A. and Coles, J. and Leonov, G. and Reboldi, A. and Buckley, C.D. and Cupedo, T. and Siebel, C. and Bayat, A. and Coles, M.C. and Ambler, C.A. (2016) 'Epidermal Notch1 recruits RORgamma+ group 3 innate lymphoid cells to orchestrate normal skin repair.', Nature communications., 7 . p. 11394.
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.
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|Publisher Web site:||http://dx.doi.org/10.1038/ncomms11394|
|Publisher statement:||This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/|
|Date accepted:||21 March 2016|
|Date deposited:||26 April 2016|
|Date of first online publication:||21 April 2016|
|Date first made open access:||26 April 2016|
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