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Scientific article
English

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

Published inImmunity, vol. 47, no. 5, p. 928-942.e7
Publication date2017
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
  • Animals
  • Humans
  • Inflammation/immunology
  • Insulin/secretion
  • Interleukin-33/biosynthesis/pharmacology
  • Islets of Langerhans/drug effects/immunology/pathology
  • Lymphocytes/drug effects/physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Cells/metabolism
  • Tretinoin/metabolism
  • Vitamin A/physiology
Citation (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. doi: 10.1016/j.immuni.2017.10.015
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Article (Published version)
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Identifiers
ISSN of the journal1074-7613
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Creation12/22/2017 12:12:00 PM
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Update time03/15/2023 7:42:09 AM
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