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 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.
Original language | English |
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Article number | 11394 |
Number of pages | 14 |
Journal | Nature Communications |
Volume | 7 |
DOIs | |
Publication status | Published - 21 Apr 2016 |
Keywords
- Animals
- Cell Movement/immunology
- Chemokine CCL20/genetics
- Chemokine CXCL13/genetics
- Epidermis/immunology
- Female
- Gene Expression Regulation
- Immunity, Innate
- Interleukin-17/genetics
- Lymphocyte Subsets/metabolism
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Inbred CBA
- Mice, Knockout
- Nuclear Receptor Subfamily 1, Group F, Member 3/deficiency
- Receptor, Notch1/genetics
- Signal Transduction/immunology
- Tumor Necrosis Factor-alpha/genetics
- Wound Healing/genetics
- Wounds, Penetrating/genetics
Profiles
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Mark Christopher Coles
- Centre for Immunology and Infection - Professor, Former employee
Person: Academic