Match!

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)
Cite
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)
Cite
References48
Newest
Published on Aug 1, 2017in Nature Communications11.88
Sandra Kallert4
Estimated H-index: 4
,
Stephanie Darbre3
Estimated H-index: 3
+ 12 AuthorsFlorian Kreppel24
Estimated H-index: 24
Viruses trigger potent cytotoxic T cell responses, whereas anti-tumour immunity has been difficult to establish. Here the authors engineer a replicating viral delivery system for tumour-associated antigens, which induces alarmin release, innate activation and protective anti-tumour immunity in mice.
Published on Nov 1, 2016in Nature Reviews Immunology44.02
Foo Y. Liew94
Estimated H-index: 94
,
Jean-Philippe Girard47
Estimated H-index: 47
,
Heth R. Turnquist14
Estimated H-index: 14
The cytokine interleukin-33 was first identified as an inducer of type 2 immune responses. It has now been shown to have pleiotropic activities on multiple immune cell types and is involved in numerous infectious and inflammatory diseases, as described in this Review.
Published on Aug 1, 2016in Cell36.22
Justin I. Odegaard26
Estimated H-index: 26
(UCSF: University of California, San Francisco),
Min-Woo Lee2
Estimated H-index: 2
(UCSF: University of California, San Francisco)
+ 6 AuthorsAjay Chawla37
Estimated H-index: 37
(UCSF: University of California, San Francisco)
Summary For placental mammals, the transition from the in utero maternal environment to postnatal life requires the activation of thermogenesis to maintain their core temperature. This is primarily accomplished by induction of uncoupling protein 1 (UCP1) in brown and beige adipocytes, the principal sites for uncoupled respiration. Despite its importance, how placental mammals license their thermogenic adipocytes to participate in postnatal uncoupled respiration is not known. Here, we provide evi...
Published on Jun 1, 2016in Nature Immunology23.53
Yoichiro Ohne2
Estimated H-index: 2
(MedImmune),
Jonathan S. Silver16
Estimated H-index: 16
(MedImmune)
+ 6 AuthorsYong-Jun Liu15
Estimated H-index: 15
(MedImmune)
Cytokines of the IL-1 family have a range of effects on innate lymphoid cells. Liu and colleagues find that IL-1 facilitates the maturation and plasticity of group 2 innate lymphoid cells.
Published on Feb 1, 2016in Diabetes, Obesity and Metabolism6.13
Steven E. Trasino5
Estimated H-index: 5
(Cornell University),
Xiao-Han Tang11
Estimated H-index: 11
(Cornell University)
+ 1 AuthorsLorraine J. Gudas48
Estimated H-index: 48
(Cornell University)
To investigate the effects of specific retinoic acid receptor (RAR) agonists in diabetes and fatty liver disease.Synthetic agonists for RARβ2 were administered to wild-type (wt) mice in a model of high-fat-diet (HFD)-induced type 2 diabetes (T2D) and to ob/ob and db/db mice (genetic models of obesity-associated T2D).We show that administration of synthetic agonists for RARβ2 to either wt mice in a model of HFD-induced T2D or to ob/ob and db/db mice reduces hyperglycaemia, peripheral insulin resi...
Published on Oct 1, 2015in Cell Metabolism22.41
Shingo Kajimura40
Estimated H-index: 40
(UCSF: University of California, San Francisco),
Bruce M. Spiegelman165
Estimated H-index: 165
(Harvard University),
Patrick Seale42
Estimated H-index: 42
(UPenn: University of Pennsylvania)
Since brown adipose tissue (BAT) dissipates energy through UCP1, BAT has garnered attention as a therapeutic intervention for obesity and metabolic diseases including type 2 diabetes. As we better understand the physiological roles of classical brown and beige adipocytes, it is becoming clear that BAT is not simply a heat-generating organ. Increased beige fat mass in response to a variety of external/internal cues is associated with significant improvements in glucose and lipid homeostasis that ...
Published on Oct 1, 2015in Current Opinion in Immunology7.67
Justin I. Odegaard26
Estimated H-index: 26
(UCSF: University of California, San Francisco),
Ajay Chawla37
Estimated H-index: 37
(UCSF: University of California, San Francisco)
Adipose tissue resident leukocytes are often cast solely as the effectors of obesity and its attendant pathologies; however, recent observations have demonstrated that these cells support and effect ‘healthy’ physiologic function as well as pathologic dysfunction. Importantly, these two disparate outcomes are underpinned by similarly disparate immune programs; type 2 responses instruct and promote metabolic normalcy, while type 1 responses drive tissue dysfunction. In this Review, we summarize t...
Published on Sep 21, 2015in Journal of Experimental Medicine10.89
Boris Calderon22
Estimated H-index: 22
,
Javier A. Carrero24
Estimated H-index: 24
+ 7 AuthorsEmil R. Unanue84
Estimated H-index: 84
We examine the features, origin, turnover, and gene expression of pancreatic macrophages under steady state. The data distinguish macrophages within distinct intrapancreatic microenvironments and suggest how macrophage phenotype is imprinted by the local milieu. Macrophages in islets of Langerhans and in the interacinar stroma are distinct in origin and phenotypic properties. In islets, macrophages are the only myeloid cells: they derive from definitive hematopoiesis, exchange to a minimum with ...
Published on Aug 1, 2015in Molecular metabolism6.18
Kimberly G. Riley2
Estimated H-index: 2
(Vandy: Vanderbilt University),
Raymond C. Pasek9
Estimated H-index: 9
(Vandy: Vanderbilt University)
+ 5 AuthorsMaureen Gannon37
Estimated H-index: 37
Objective Promotion of endogenous β-cell mass expansion could facilitate regeneration in patients with diabetes. We discovered that the secreted protein CTGF (aka CCN2) promotes adult β-cell replication and mass regeneration after injury via increasing β-cell immaturity and shortening the replicative refractory period. However, the mechanism of CTGF-mediated β-cell proliferation is unknown. Here we focused on whether CTGF alters cells of the immune system to enhance β-cell replication.
Published on Jul 1, 2015in Immunity21.52
Ari B. Molofsky17
Estimated H-index: 17
(UCSF: University of California, San Francisco),
Frédéric Van Gool12
Estimated H-index: 12
(UCSF: University of California, San Francisco)
+ 5 AuthorsRichard M. Locksley88
Estimated H-index: 88
(UCSF: University of California, San Francisco)
Summary Group 2 innate lymphoid cells (ILC2s) and regulatory T (Treg) cells are systemically induced by helminth infection but also sustain metabolic homeostasis in adipose tissue and contribute to tissue repair during injury. Here we show that interleukin-33 (IL-33) mediates activation of ILC2s and Treg cells in resting adipose tissue, but also after helminth infection or treatment with IL-2. Unexpectedly, ILC2-intrinsic IL-33 activation was required for Treg cell accumulation in vivo and was i...
Cited By20
Newest
Published on Aug 1, 2019in International Immunopharmacology3.36
Keying Zhang , Jing Yang3
Estimated H-index: 3
(PRC: China Medical University (PRC))
+ 4 AuthorsJian Du3
Estimated H-index: 3
Abstract The incidence and mortality of type 2 diabetes mellitus (T2DM) rank among the top ten worldwide. Emerging studies indicate pathological roles for the immune system in inflammation, insulin resistance and islet β-cell damage in subjects with T2DM. Methionine enkephalin (MENK) is present in endocrine cells of the pancreas and has been suggested to be an important mediator between the immune and neuroendocrine systems. Therefore, it may play a role in modulating insulin secretion from isle...
Published on Apr 25, 2019in Endocrine Reviews15.17
Marc Y. Donath57
Estimated H-index: 57
(University of Basel),
Daniel T. Meier2
Estimated H-index: 2
(University of Basel),
Marianne Böni-Schnetzler21
Estimated H-index: 21
(University of Basel)
Published on Apr 5, 2019in Seminars in Immunopathology6.80
Elise Dalmas (Paris Diderot University)
Growing evidence suggests that components of the innate immune system play a crucial role in regulating metabolic homeostasis. Macrophages were the primary immune cells to be described in both the white adipose tissue and the pancreatic islets. Therein, their functions, beneficial or detrimental, are extending under steady state and in the context of obesity-induced type 2 diabetes. Other populations, including innate lymphoid cells, are emerging as key sentinels of metabolic tissues and privile...
Published on Apr 15, 2019in Seminars in Immunopathology6.80
Marianne Böni-Schnetzler21
Estimated H-index: 21
(University Hospital of Basel),
Daniel T. Meier (University Hospital of Basel)
Metabolic diseases including type 2 diabetes are associated with meta-inflammation. β-Cell failure is a major component of the pathogenesis of type 2 diabetes. It is now well established that increased numbers of innate immune cells, cytokines, and chemokines have detrimental effects on islets in these chronic conditions. Recently, evidence emerged which points to initially adaptive and restorative functions of inflammatory factors and immune cells in metabolism. In the following review, we prov...
Published on Jun 27, 2019in Journal of Experimental Medicine10.89
Batika M.J. Rana2
Estimated H-index: 2
(LMB: Laboratory of Molecular Biology),
Eric Jou (LMB: Laboratory of Molecular Biology)+ 17 AuthorsAydan Szeto (LMB: Laboratory of Molecular Biology)
Published on May 1, 2019in Mucosal Immunology7.35
Tao Liu9
Estimated H-index: 9
(Brigham and Women's Hospital),
Nora A. Barrett14
Estimated H-index: 14
(Harvard University)
+ 7 AuthorsJoshua A. Boyce48
Estimated H-index: 48
(Harvard University)
Cysteinyl leukotrienes (cysLTs) facilitate eosinophilic mucosal type 2 immunopathology, especially in aspirin-exacerbated respiratory disease (AERD), by incompletely understood mechanisms. We now demonstrate that platelets, activated through the type 2 cysLT receptor (CysLT2R), cause IL-33-dependent immunopathology through a rapidly inducible mechanism requiring the actions of high mobility box 1 (HMGB1) and the receptor for advanced glycation end products (RAGE). Leukotriene C4 (LTC4) induces s...
Published on May 1, 2019in International Immunopharmacology3.36
Jingli Lu2
Estimated H-index: 2
(Zhengzhou University),
Yan Liang2
Estimated H-index: 2
(Zhengzhou University)
+ 2 AuthorsXiaojian Zhang3
Estimated H-index: 3
(Zhengzhou University)
Abstract IL-33/ST2 signal is important for the generation of forkhead box P3 (Foxp3) + regulatory (Treg) cells, which contribute to immune homeostasis in the context of diseases. The aim of this study was to determine whether targeting IL-33/ST2 signal could establish immunological tolerance and prevent type 1 diabetes (T1D) in nonobese diabetic (NOD) mice. Female NOD mice treated with IL-33 for 4 weeks decreased the incidence and delayed the onset of autoimmune diabetes, whereas IL-33 did not r...
Published on May 1, 2019in Pharmacology & Therapeutics9.40
William S. Blaner60
Estimated H-index: 60
(Columbia University)
Abstract Much evidence has accumulated in the literature over the last fifteen years that indicates vitamin A has a role in metabolic disease prevention and causation. This literature proposes that vitamin A can affect obesity development and the development of obesity-related diseases including insulin resistance, type 2 diabetes, hepatic steatosis and steatohepatitis, and cardiovascular disease. Retinoic acid, the transcriptionally active form of vitamin A, accounts for many of the reported as...
Published on May 1, 2019in Seminars in Immunology7.36
Adeline Crinier3
Estimated H-index: 3
,
Eric Vivier87
Estimated H-index: 87
,
Mathieu Blery18
Estimated H-index: 18
Abstract Immunotherapies have revolutionized cancer treatment over the last 20 years. They aim either to boost immune cell activation or decrease immune cell inhibition, to improve control over cancer development. Various strategies for improving tumor immunity have been tested. Some have been approved and others are currently in clinical trials. They target the immune system itself, the tumor cells or the microenvironment. Most focus on enhancing T-cell responses, notably through infusions of a...
Published on Mar 1, 2019in Immunity21.52
Madelene W. Dahlgren4
Estimated H-index: 4
(UCSF: University of California, San Francisco),
Stephen W. Jones1
Estimated H-index: 1
(UCSF: University of California, San Francisco)
+ 11 AuthorsAnna V. Molofsky13
Estimated H-index: 13
(UCSF: University of California, San Francisco)
Summary Type 2 lymphocytes promote both physiologic tissue remodeling and allergic pathology, yet their physical tissue niches are poorly described. Here, we used quantitative imaging to define the tissue niches of group 2 innate lymphoid cells (ILC2s), which are critical instigators of type 2 immunity. We identified a dominant adventitial niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells. However, ILC2s were ...