The neuropeptide VIP confers anticipatory mucosal immunity by regulating ILC3 activity
Top Cited Papers
- 23 December 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 21 (2), 168-177
- https://doi.org/10.1038/s41590-019-0567-y
Abstract
Group 3 innate lymphoid cell (ILC3)-mediated production of the cytokine interleukin-22 (IL-22) is critical for the maintenance of immune homeostasis in the gastrointestinal tract. Here, we find that the function of ILC3s is not constant across the day, but instead oscillates between active phases and resting phases. Coordinate responsiveness of ILC3s in the intestine depended on the food-induced expression of the neuropeptide vasoactive intestinal peptide (VIP). Intestinal ILC3s had high expression of the G protein-coupled receptor vasoactive intestinal peptide receptor 2 (VIPR2), and activation by VIP markedly enhanced the production of IL-22 and the barrier function of the epithelium. Conversely, deficiency in signaling through VIPR2 led to impaired production of IL-22 by ILC3s and increased susceptibility to inflammation-induced gut injury. Thus, intrinsic cellular rhythms acted in synergy with the cyclic patterns of food intake to drive the production of IL-22 and synchronize protection of the intestinal epithelium through a VIP–VIPR2 pathway in ILC3s.Keywords
Funding Information
- Department of Health | National Health and Medical Research Council (APP1135898, APP1165443, APP1122277, APP1054925, APP1054925, APP1123000, APP1154970)
- Cure Cancer Australia Foundation (APP1163990)
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