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

Published on Nov 1, 2017in Immunity21.52
· DOI :10.1016/j.immuni.2017.10.015
Elise Dalmas7
Estimated H-index: 7
(University of Basel),
Frank M. Lehmann2
Estimated H-index: 2
(University of Basel)
+ 18 AuthorsMarc Y. Donath57
Estimated H-index: 57
(University of Basel)
Abstract
Summary 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.
  • References (48)
  • Citations (20)
References48
Newest
#1Justin I. Odegaard (UCSF: University of California, San Francisco)H-Index: 26
#2Min-Woo Lee (UCSF: University of California, San Francisco)H-Index: 2
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#1Shingo Kajimura (UCSF: University of California, San Francisco)H-Index: 40
#2Bruce M. Spiegelman (Harvard University)H-Index: 166
Last.Patrick Seale (UPenn: University of Pennsylvania)H-Index: 42
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#1Justin I. Odegaard (UCSF: University of California, San Francisco)H-Index: 26
#2Ajay Chawla (UCSF: University of California, San Francisco)H-Index: 37
#1Kimberly G. Riley (Vandy: Vanderbilt University)H-Index: 2
#2Raymond C. Pasek (Vandy: Vanderbilt University)H-Index: 9
Last.Maureen GannonH-Index: 37
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#1Ari B. Molofsky (UCSF: University of California, San Francisco)H-Index: 17
#2Frédéric Van Gool (UCSF: University of California, San Francisco)H-Index: 12
Last.Richard M. Locksley (UCSF: University of California, San Francisco)H-Index: 89
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#1Madelene W. Dahlgren (UCSF: University of California, San Francisco)H-Index: 4
#2Ari B. Molofsky (UCSF: University of California, San Francisco)H-Index: 17
#1Marc Y. Donath (University of Basel)H-Index: 57
#2Charles A. Dinarello (CU: University of Colorado Boulder)H-Index: 173
Last.Thomas Mandrup-Poulsen (UCPH: University of Copenhagen)H-Index: 64
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#1Batika M.J. Rana (LMB: Laboratory of Molecular Biology)H-Index: 2
#2Eric Jou (LMB: Laboratory of Molecular Biology)
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#1Marc Y. Donath (University of Basel)H-Index: 57
#2Daniel T. Meier (University of Basel)H-Index: 2
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