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Title

Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production

Authors
Dalmas, Elise
Lehmann, Frank M
Dror, Erez
Wueest, Stephan
Thienel, Constanze
Borsigova, Marcela
Stawiski, Marc
Traunecker, Emmanuel
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Published in Immunity. 2017, vol. 47, no. 5, p. 928-942.e7
Abstract Pancreatic-islet inflammation contributes to the failure of β cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and enhanced by a diabetes milieu (glucose, IL-1β, and palmitate). IL-33 promoted β cell function through islet-resident group 2 innate lymphoid cells (ILC2s) that elicited retinoic acid (RA)-producing capacities in macrophages and dendritic cells via the secretion of IL-13 and colony-stimulating factor 2. In turn, local RA signaled to the β cells to increase insulin secretion. This IL-33-ILC2 axis was activated after acute β cell stress but was defective during chronic obesity. Accordingly, IL-33 injections rescued islet function in obese mice. Our findings provide evidence that an immunometabolic crosstalk between islet-derived IL-33, ILC2s, and myeloid cells fosters insulin secretion.
Keywords AnimalsHumansInflammation/immunologyInsulin/secretionInterleukin-33/biosynthesis/pharmacologyIslets of Langerhans/drug effects/immunology/pathologyLymphocytes/drug effects/physiologyMaleMiceMice, Inbred BALB CMice, Inbred C57BLMyeloid Cells/metabolismTretinoin/metabolismVitamin A/physiology
Identifiers
PMID: 29166590
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Article (Published version) (3.4 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Mitochondries et sécrétion d'insuline (671)
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(ISO format)
DALMAS, Elise et al. Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production. In: Immunity, 2017, vol. 47, n° 5, p. 928-942.e7. https://archive-ouverte.unige.ch/unige:100806

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Deposited on : 2017-12-22

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