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Nat Immunol. 2019 Dec 23. doi: 10.1038/s41590-019-0567-y. [Epub ahead of print]

The neuropeptide VIP confers anticipatory mucosal immunity by regulating ILC3 activity.

Author information

1
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. seillet@wehi.edu.au.
2
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia. seillet@wehi.edu.au.
3
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
4
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
5
School of Mathematics and Statistics, University of Melbourne, Melbourne, Victoria, Australia.
6
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. belz@wehi.edu.au.
7
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia. belz@wehi.edu.au.
8
Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia. belz@wehi.edu.au.

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.

PMID:
31873294
DOI:
10.1038/s41590-019-0567-y

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