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

doi:10.1038/ncomms11394

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

Hematology

Research output: Contribution to journal › Article › Academic › peer-review

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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 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 language	Undefined/Unknown
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11394
Publication status	Published - 2016

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EMC MM-02-41-04

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10.1038/ncomms11394

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Cite this

Li, Z., Hodgkinson, T., Gothard, EJ., Boroumand, S., Lamb, R., Cummins, I., Narang, P., Sawtell, A., Coles, J., Leonov, G., Reboldi, A., Buckley, CD., Cupedo, T., Siebel, C., Bayat, A., Coles, MC., & Ambler, CA. (2016). Epidermal Notch1 recruits ROR gamma(+) group 3 innate lymphoid cells to orchestrate normal skin repair. Nature Communications, 7. https://doi.org/10.1038/ncomms11394

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title = "Epidermal Notch1 recruits ROR gamma(+) 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 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.",

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

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Li, Z, Hodgkinson, T, Gothard, EJ, Boroumand, S, Lamb, R, Cummins, I, Narang, P, Sawtell, A, Coles, J, Leonov, G, Reboldi, A, Buckley, CD, Cupedo, T, Siebel, C, Bayat, A, Coles, MC & Ambler, CA 2016, 'Epidermal Notch1 recruits ROR gamma(+) group 3 innate lymphoid cells to orchestrate normal skin repair', Nature Communications, vol. 7. https://doi.org/10.1038/ncomms11394

TY - JOUR

T1 - Epidermal Notch1 recruits ROR gamma(+) group 3 innate lymphoid cells to orchestrate normal skin repair

AU - Li, Z

AU - Hodgkinson, T

AU - Gothard, EJ

AU - Boroumand, S

AU - Lamb, R

AU - Cummins, I

AU - Narang, P

AU - Sawtell, A

AU - Coles, J

AU - Leonov, G

AU - Reboldi, A

AU - Buckley, CD

AU - Cupedo, Tom

AU - Siebel, C

AU - Bayat, A

AU - Coles, MC

AU - Ambler, CA

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms11394

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