Epidermal Notch1 Recruits RORγ+ Group 3 Innate Lymphoid Cells to Orchestrate Normal Skin Repair

The study demonstrated that epidermal Notch1 played a crucial role in skin repair by recruiting RORγ+ group 3 innate lymphoid cells (ILC3s) to wound sites. Notch1 activation increased significantly after skin injury, peaking at 4 days post-wounding, and was primarily active in suprabasal epidermal keratinocytes. This activation led to the recruitment of ILC3s, which were rare in uninjured skin, through a TNFα-dependent process. ILC3s were shown to produce IL17F and CCL3, crucial for normal healing, as they controlled epidermal proliferation and macrophage entry. Mice deficient in RORγ+ ILC3s exhibited poor wound healing due to delayed epidermal proliferation and macrophage recruitment. The findings suggested that Notch1 was a key signal in skin epithelium for driving innate immune cell recruitment and facilitating normal skin tissue repair.