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Interleukin-33 and Interferon-γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation

Published on Jul 1, 2015in Immunity21.52
· DOI :10.1016/j.immuni.2015.05.019
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. Locksley89
Estimated H-index: 89
(UCSF: University of California, San Francisco)
Cite
Abstract
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 independent of ILC2 type 2 cytokines but partially dependent on direct co-stimulatory interactions via ICOSL-ICOS. IFN-γ inhibited ILC2 activation and Treg cell accumulation by IL-33 in infected tissue, as well as adipose tissue, where repression increased with aging and high-fat diet-induced obesity. IL-33 and ILC2s are central mediators of type 2 immune responses that promote tissue and metabolic homeostasis, and IFN-γ suppresses this pathway, likely to promote inflammatory responses and divert metabolic resources necessary to protect the host.
  • References (65)
  • Citations (155)
Cite
References65
Newest
Published on Jul 1, 2015in The FASEB Journal5.39
Leonie Hussaarts8
Estimated H-index: 8
(LUMC: Leiden University Medical Center),
Noemí García-Tardón1
Estimated H-index: 1
(LUMC: Leiden University Medical Center)
+ 9 AuthorsVanessa van Harmelen13
Estimated H-index: 13
(LUMC: Leiden University Medical Center)
Chronic low-grade inflammation associated with obesity contributes to insulin resistance and type 2 diabetes. Helminth parasites are the strongest natural inducers of type 2 immune responses, and short-lived infection with rodent nematodes was reported to improve glucose tolerance in obese mice. Here, we investigated the effects of chronic infection (12 weeks) with Schistosoma mansoni, a helminth that infects millions of humans worldwide, on whole-body metabolic homeostasis and white adipose tis...
Published on Apr 1, 2015in Nature Immunology23.53
Felix M. Wensveen18
Estimated H-index: 18
(University of Rijeka),
Vedrana Jelenčić5
Estimated H-index: 5
(University of Rijeka)
+ 10 AuthorsF. Thomas Wunderlich19
Estimated H-index: 19
(MPG: Max Planck Society)
Visceral adipose tissue (VAT) inflammation drives obesity-induced insulin resistance. Polic and colleagues show that VAT NK cells sense obesity-induced adipose tissue stress and drive inflammation through the production of interferon-γ.
Published on Mar 1, 2015in Immunity21.52
Hadi Maazi11
Estimated H-index: 11
(SC: University of Southern California),
Nisheel Patel3
Estimated H-index: 3
(SC: University of Southern California)
+ 6 AuthorsOmid Akbari34
Estimated H-index: 34
(SC: University of Southern California)
Summary Allergic asthma is caused by Th2-cell-type cytokines in response to allergen exposure. Type 2 innate lymphoid cells (ILC2s) are a newly identified subset of immune cells that, along with Th2 cells, contribute to the pathogenesis of asthma by producing copious amounts of IL-5 and IL-13, which cause eosinophilia and airway hyperreactivity (AHR), a cardinal feature of asthma. ILC2s express ICOS, a T cell costimulatory molecule with a currently unknown function. Here we showed that a lack of...
Published on Mar 1, 2015in Journal of Immunology4.72
R. Lee Reinhardt82
Estimated H-index: 82
,
Hong-Erh Liang22
Estimated H-index: 22
(UCSF: University of California, San Francisco)
+ 4 AuthorsRichard M. Locksley89
Estimated H-index: 89
(UCSF: University of California, San Francisco)
Autoinflammatory disease and hyperinflammatory syndromes represent a growing number of diseases associated with inappropriately controlled inflammation in multiple organs. Systemic inflammation commonly results from dysregulated activation of innate immune cells, and therapeutic targeting of the IL-1β pathway has been used to ameliorate some of these diseases. Some hyperinflammatory syndromes, however, such as hemophagocytic lymphohistiocytosis and the newly classified proteasome disability synd...
Published on Mar 1, 2015in Nature Immunology23.53
Ajithkumar Vasanthakumar12
Estimated H-index: 12
(University of Melbourne),
Kazuyo Moro18
Estimated H-index: 18
(YCU: Yokohama City University)
+ 18 AuthorsSeth L. Masters36
Estimated H-index: 36
(University of Melbourne)
Obesity-associated inflammation is restrained by regulatory T cells present in visceral fat. Kallies and colleagues show interleukin 33 and the transcription factors BATF and IRF4 are necessary to maintain visceral adipose tissue Treg cells.
Published on Mar 1, 2015in Nature43.07
Jonathan R. Brestoff14
Estimated H-index: 14
,
Brian S. Kim23
Estimated H-index: 23
+ 8 AuthorsDavid Artis78
Estimated H-index: 78
Group 2 innate lymphoid cells are shown to have a critical role in energy homeostasis by producing methionine-enkephalin peptides in response to interleukin 33, thus promoting the beiging of white adipose tissue; increased numbers of beige (also known as brown-like or brite) fat cells in white adipose tissue leads to increased energy expenditure and decreased adiposity.
Published on Mar 1, 2015in Nature Immunology23.53
Michelle L. Robinette12
Estimated H-index: 12
,
Anja Fuchs25
Estimated H-index: 25
+ 5 AuthorsMarco Colonna109
Estimated H-index: 109
The classification of some subsets of innate lymphoid cells (ILCs) is unclear. Colonna and colleagues use transcriptional profiling to show unique gene-expression patterns for some ILCs and overlapping patterns between ILC1 and NK cells.
Published on Feb 1, 2015in Neuron14.40
Sachin P. Gadani9
Estimated H-index: 9
,
James T. Walsh9
Estimated H-index: 9
+ 2 AuthorsJonathan Kipnis53
Estimated H-index: 53
SUMMARY Inflammation is a prominent feature of CNS injury that heavily influences neuronal survival, yet the signals that initiate and control it remain poorly understood. Here we identify the nuclear alarmin, interleukin (IL)-33, as an important regulator of the innate immune response after CNS injury. IL-33 is expressed widely throughout the healthy brain and is concentrated in white mater due to predominant expression in post-mitotic oligodendrocytes. IL-33 is released immediately after CNS i...
Published on Jan 1, 2015in Cell36.22
Min-Woo Lee2
Estimated H-index: 2
(UCSF: University of California, San Francisco),
Justin I. Odegaard26
Estimated H-index: 26
(UCSF: University of California, San Francisco)
+ 6 AuthorsAjay Chawla37
Estimated H-index: 37
(UCSF: University of California, San Francisco)
Summary Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanisticall...
Published on Jan 1, 2015in Nature Immunology23.53
Lydia Lynch23
Estimated H-index: 23
,
Xavier Michelet9
Estimated H-index: 9
+ 12 AuthorsHui-Fern Koay3
Estimated H-index: 3
iNKT cells in adipose tissue are anti-inflammatory. Brenner and colleagues show that adipose iNKT cells have a unique transcriptional program, produce IL-2 and IL-10 and lack expression of the transcription factor PLZF.
Cited By155
Newest
Published on Mar 4, 2019in Scientific Reports4.01
Bárbara M. Oliveira (University of Porto), Alexandra Correia14
Estimated H-index: 14
(IBMC: Instituto de Biologia Molecular e Celular)
+ 4 AuthorsLuzia Teixeira9
Estimated H-index: 9
(University of Porto)
The importance of immune cells present in the adipose tissue to metabolic homeostasis has been increasingly recognized. Nevertheless, in bovines few studies have so far addressed the immune cell populations resident in this tissue. Here we developed an eight-colour flow cytometry panel to address T cell populations present in bovine adipose tissue. Our results showed that γδ T cells, CD4+ and CD8+ CD3+ non-γδ T cells, as well as NK cells, are present in the mesenteric and subcutaneous adipose ti...
Published on 2019in Nature Reviews Immunology44.02
Gregory F. Sonnenberg27
Estimated H-index: 27
(Cornell University),
Matthew R. Hepworth20
Estimated H-index: 20
(MAHSC: Manchester Academic Health Science Centre)
Innate lymphoid cells (ILCs) are enriched at barrier surfaces of the mammalian body where they rapidly respond to host, microbial or environmental stimuli to promote immunity or tissue homeostasis. Furthermore, ILCs are dysregulated in multiple human diseases. Over the past decade, substantial advances have been made in identifying the heterogeneity and functional diversity of ILCs, which have revealed striking similarities to T cell subsets. However, emerging evidence indicates that ILCs also h...
Published on 2019in Journal of Experimental Medicine10.89
Roberto R. Ricardo-Gonzalez10
Estimated H-index: 10
(UCSF: University of California, San Francisco),
Richard M. Locksley89
Estimated H-index: 89
(UCSF: University of California, San Francisco)
Published on 2019in Immunological Reviews11.29
Vincent Panneton2
Estimated H-index: 2
(UdeM: Université de Montréal),
Jinsam Chang3
Estimated H-index: 3
(UdeM: Université de Montréal)
+ 2 AuthorsWoong-Kyung Suh18
Estimated H-index: 18
Published on 2019in Trends in Immunology13.00
Harry Kane (Trinity College, Dublin), Lydia Lynch23
Estimated H-index: 23
(Trinity College, Dublin)
Adipose tissue is a critical regulator of systemic metabolism and normal bodily homeostasis. Recently, the immune system has been implicated in the regulation of adipose tissue homeostasis and function. Here, we highlight new insights into the distinct phenotypes and functions of adipose resident leukocytes, including a growing body of work on their role in adipose tissue remodeling and thermogenesis. We discuss how the protective capacity of the adipose immune system can be diminished during ob...
Published on Sep 1, 2019in Trends in Immunology13.00
Madelene W. Dahlgren4
Estimated H-index: 4
(UCSF: University of California, San Francisco),
Ari B. Molofsky17
Estimated H-index: 17
(UCSF: University of California, San Francisco)
Inflammation must be effective, while limiting excessive tissue damage. To walk this line, immune functions are grossly compartmentalized by innate cells that act locally and adaptive cells that function systemically. But what about the myriad tissue-resident immune cells that are critical to this balancing act and lie on a spectrum of innate and adaptive immunity? We propose that mammalian perivascular adventitial ‘cuffs' are conserved sites in multiple organs, enriched for these tissue-residen...
Published on Jan 1, 2019in Frontiers in Immunology4.72
Claudia Baumann (FU: Free University of Berlin), Anja Fröhlich (FU: Free University of Berlin)+ 3 AuthorsMax Löhning (FU: Free University of Berlin)
Memory CD8+ cytotoxic T lymphocytes (CTLs) can protect against viral reinfection. However, the signals driving rapid memory CTL reactivation have remained ill-defined. Viral infections can trigger the release of the alarmin interleukin-33 (IL-33) from non-hematopoietic cells. IL-33 signals through its unique receptor ST2 to promote primary effector expansion and activation of CTLs. Here, we show that the transcription factor STAT4 regulated the expression of ST2 on CTLs in vitro and in vivo in p...
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 Jun 26, 2019in Immunotherapy3.03
Shunfeng Hu (SDU: Shandong University), Xin Wang
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