Journal article

The neuropeptide VIP confers anticipatory mucosal immunity by regulating ILC3 activity

Cyril Seillet, Kylie Luong, Julie Tellier, Nicolas Jacquelot, Rui Dong Shen, Peter Hickey, Verena C Wimmer, Lachlan Whitehead, Kelly Rogers, Gordon K Smyth, Alexandra L Garnham, Matthew E Ritchie, Gabrielle T Belz



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. Conv..

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Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by Cure Cancer and Cancer Australia

Awarded by NHMRC

Funding Acknowledgements

We thank M. Camilleri, A. Lin, S. Cree, C. Alvarado and T. Putoczki for expert technical advice and support. We thank S. Wilcox for performing the sequencing, and S. Nutt for critical reading of the manuscript. Financial support for this work was provided by National Health and Medical Research Council (NHMRC) of Australia grants (APP1165443, 1122277 and 1054925 to G.T.B. and C.S.), Cure Cancer and Cancer Australia (APP1163990 to N.J.), The Rebecca L. Cooper Medical Research Foundation (to G.T.B.) and fellowships from the NHMRC (APP1135898 to G.T.B., APP1123000 to C.S. and APP1154970 to G.K.S.). This study was made possible through the Victorian State Government Operational Infrastructure Support Program and the Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme.X