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

April 2016 in “ Nature Communications ”

Zhi Li, Tom Hodgkinson, Elizabeth J. Gothard, Soulmaz Boroumand, Rebecca Lamb, Ian Cummins, Priyanka Narang, Amy Sawtell, Jenny Coles, German Leonov, Andrea Reboldi, Christopher D. Buckley, Tom Cupedo, Christian W. Siebel, Ardeshir Bayat, Mark Coles, Carrie A. Ambler

Notch1 RORγ+ group 3 innate lymphoid cells ILC3s TNFα IL17F CCL3 epidermal keratinocytes macrophage group 3 innate lymphoid cells tumor necrosis factor alpha interleukin 17F chemokine ligand 3 skin cells immune cells

TLDR Notch1 helps skin heal by attracting specific immune cells.

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.