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

被引：149

作者：

Dalmas, Elise ^{[1
,2
]}

Lehmann, Frank M. ^{[2
,3
]}

Dror, Erez ^{[1
,2
]}

Wueest, Stephan ^{[4
,5
]}

Thienel, Constanze ^{[1
,2
]}

Borsigova, Marcela ^{[1
,2
]}

Stawiski, Marc ^{[1
,2
]}

Traunecker, Emmanuel ^{[2
]}

Lucchini, Fabrizio C. ^{[4
,5
]}

Dapito, Dianne H. ^{[6
]}

Kallert, Sandra M. ^{[2
]}

Guigas, Bruno ^{[7
,8
]}

Pattou, Francois ^{[9
]}

Kerr-Conte, Julie ^{[9
]}

Maechler, Pierre ^{[10
,11
]}

Girard, Jean-Philippe ^{[12
]}

Konrad, Daniel ^{[4
,5
]}

Wolfrum, Christian ^{[6
]}

Boni-Schnetzler, Marianne ^{[1
,2
]}

Finke, Daniela ^{[2
,3
]}

Donath, Marc Y. ^{[1
,2
]}

机构：

[1] Univ Hosp Basel, Clin Endocrinol Diabet & Metab, CH-4031 Basel, Switzerland

[2] Univ Basel, Dept Biomed, CH-4031 Basel, Switzerland

[3] Univ Basel, Childrens Hosp, CH-4056 Basel, Switzerland

[4] Univ Childrens Hosp, Dept Pediat Endocrinol & Diabetol, Steinwiesstr 75, CH-8032 Zurich, Switzerland

[5] Univ Childrens Hosp, Childrens Res Ctr, Steinwiesstr 75, CH-8032 Zurich, Switzerland

[6] Swiss Fed Inst Technol, Inst Food Nutr & Hlth, Schorenstr 16, CH-8603 Schwerzenbach, Switzerland

[7] Leiden Univ, Med Ctr, Dept Parasitol, NL-2333 Leiden, Netherlands

[8] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2333 Leiden, Netherlands

[9] Univ Lille, INSERM, CHU Lille,EGID, Translat Res Diabet U119,European Genom Inst Diab, F-59000 Lille, France

[10] Univ Geneva, Med Ctr, Dept Cell Physiol & Metab, Geneva, Switzerland

[11] Univ Geneva, Med Ctr, Fac Diabet Ctr, Geneva, Switzerland

[12] Univ Toulouse, Inst Pharmacol & Biol Struct, CNRS, UPS, F-31077 Toulouse, France

来源：

IMMUNITY | 2017年 / 47卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

VISCERAL ADIPOSE-TISSUE; VITAMIN-A-DEFICIENCY; DENDRITIC CELLS; GLYCEMIC CONTROL; GENE-EXPRESSION; MACROPHAGES; INFLAMMATION; OBESITY; IL-33; PROLIFERATION;

D O I：

10.1016/j.immuni.2017.10.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Pancreatic-islet inflammation contributes to the failure of beta 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-1 beta, and palmitate). IL-33 promoted b 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 b cells to increase insulin secretion. This IL-33-ILC2 axis was activated after acute b 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 isletderived IL-33, ILC2s, and myeloid cells fosters insulin secretion.

引用

页码：928 / +

页数：22

共 48 条

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Free Fatty Acids Induce a Proinflammatory Response in Islets via the Abundantly Expressed Interleukin-1 Receptor I [J].