Vasoactive intestinal peptide confers anticipatory mucosal immunity by regulating ILC3 activity

Seillet, C.; Luong, K.; Tellier, J.; Jacquelot, N.; Shen, R. D.; Hickey, P.; Wimmer, V. C.; Whitehead, L.; Rogers, K.; Smyth, G.; Garnham, A.; Ritchie, M. E.; Belz, G.

doi:10.1101/729400

bioRxiv · 10.1101/729400

Vasoactive intestinal peptide confers anticipatory mucosal immunity by regulating ILC3 activity

Seillet, C.·Luong, K.·Tellier, J.·Jacquelot, N.·Shen, R. D.·Hickey, P.·Wimmer, V. C.·Whitehead, L.·Rogers, K.·Smyth, G.·Garnham, A.·Ritchie, M. E.·Belz, G.

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Abstract

ILC3-mediated IL-22 cytokine production is critical for the maintenance of immune homeostasis in the gastrointestinal tract. Here, we show that group 3 ILC (ILC3) constitutive function is not constant across the day but instead oscilliates between active and resting phases. Coordinate responsiveness of ILC3 in the intestine depended on food-induced expression of the neuronal hormone vasoactive intestinal peptide (VIP). Intestinal ILC3 expressed high levels of the G protein-coupled receptor, VIPR2, and activation via enteric neuronal VIP markedly enhanced IL-22 production and conferred gut protection. Conversely, deficiency of VIPR2 signalling led to impaired production of IL-22 by ILC3 and increased susceptibility to inflammatory gut disease. As such, intrinsic cellular rhythms synergise with the cyclic patterns of food intake to drive IL-22 thereby syncronizing intestinal epithelial protection via the ILC3 VIP-VIPR2 pathway.

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Seillet, C., Luong, K., Tellier, J., Jacquelot, N., Shen, R. D., Hickey, P., Wimmer, V. C., Whitehead, L., Rogers, K., Smyth, G., Garnham, A., Ritchie, M. E., Belz, G.. 2019-08-08. Vasoactive intestinal peptide confers anticipatory mucosal immunity by regulating ILC3 activity. https://doi.org/10.1101/729400

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