Abstract：
:High-fat diet (HFD) and inflammation are key contributors to insulin resistance and type 2 diabetes (T2D). Interleukin (IL)-1β plays a role in insulin resistance, yet how IL-1β is induced by the fatty acids in an HFD, and how this alters insulin signaling, is unclear. We show that the saturated fatty acid palmitate, but not unsaturated oleate, induces the activation of the NLRP3-ASC inflammasome, causing caspase-1, IL-1β and IL-18 production. This pathway involves mitochondrial reactive oxygen species and the AMP-activated protein kinase and unc-51-like kinase-1 (ULK1) autophagy signaling cascade. Inflammasome activation in hematopoietic cells impairs insulin signaling in several target tissues to reduce glucose tolerance and insulin sensitivity. Furthermore, IL-1β affects insulin sensitivity through tumor necrosis factor-independent and dependent pathways. These findings provide insights into the association of inflammation, diet and T2D.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Wen H,Gris D,Lei Y,Jha S,Zhang L,Huang MT,Brickey WJ,Ting JPdoi
10.1038/ni.2022subject
Has Abstractpub_date
2011-05-01 00:00:00pages
408-15issue
5eissn
1529-2908issn
1529-2916pii
ni.2022journal_volume
12pub_type
杂志文章abstract：:Two potential outcomes confront proliferating antigen-stimulated naive T cells: differentiation to effector and memory cells, or deletion. How stimulation affects cell fate is unclear. Autonomous CD8+ T cell differentiation has been proposed, but this does not explain the abortive proliferation of T cells induced by i...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni908
更新日期：2003-04-01 00:00:00
abstract：:Ingested antigens lead to the generation of effector T cells that secrete interleukin 4 (IL-4) rather than interferon-gamma (IFN-gamma) and are capable of influencing naive T cells in their immediate environment to do the same. Using chimeric mice generated by aggregation of two genotypically different embryos, we fou...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1077
更新日期：2004-06-01 00:00:00
abstract：:Group 2 innate lymphoid cells (ILC2s) and CD4+ type 2 helper T cells (TH2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and TH2 cells differentiated independently but shared overlapping effector function programs that were m...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3582
更新日期：2016-12-01 00:00:00
abstract：:EAE can refer either to experimental autoimmune encephalomyelitis or experimental allergic encephalomyelitis. Although EAE is classically a prototypic T helper 1 (TH1) cell-mediated autoimmune disease, it can also be induced by TH2 cells. Characteristically, the most severe manifestation of allergy, anaphylaxis, is as...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/85266
更新日期：2001-03-01 00:00:00
abstract：:High-affinity antibodies are critical for host protection and underlie successful vaccines. The generation of such antibodies requires T cell-dependent help, which mediates germinal center reactions in which mutation and selection of B cells occurs. Using an interleukin 4-reporter system, we show here that CD4(+) foll...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.1715
更新日期：2009-04-01 00:00:00
abstract：:We used high-resolution mass spectrometry to map the cytotoxic T lymphocyte (CTL) proteome and the effect of the metabolic checkpoint kinase mTORC1 on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes, and mTORC1 selectively repressed and promoted expression of a subset of CTL proteins (~10%)....
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3314
更新日期：2016-01-01 00:00:00
abstract：:CD8(+) T cells eliminate intracellular infections through two contact-dependent effector functions: cytolysis and secretion of antiviral cytokines. Here we identify the following additional function for memory CD8(+) T cells that persist at front-line sites of microbial exposure: to serve as local sensors of previousl...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2568
更新日期：2013-05-01 00:00:00
abstract：:The mechanisms that lead to inflammation after necrotic cell death are poorly understood. New data show that the C-type lectin Mincle is involved in this process. ...
journal_title：Nature immunology
pub_type： 评论,杂志文章,评审
doi：10.1038/ni1008-1099
更新日期：2008-10-01 00:00:00
abstract：:Autoreactive B cells have critical roles in a large diversity of autoimmune diseases, but the molecular pathways that control these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed microRNA library and identified miR-148a as a potent regulator of B cell tolerance. Ele...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3385
更新日期：2016-04-01 00:00:00
abstract：:Chronic inflammation is a common feature of obesity, with elevated cytokines such as interleukin-1 (IL-1) in the circulation and tissues. Here, we report an unconventional IL-1R-MyD88-IRAK2-PHB/OPA1 signaling axis that reprograms mitochondrial metabolism in adipocytes to exacerbate obesity. IL-1 induced recruitment of...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-020-0750-1
更新日期：2020-10-01 00:00:00
abstract：:PD-1, a negative coreceptor expressed on antigen-stimulated T cells and B cells, seems to serve as a 'rheostat' of the immune response. The molecular mechanisms of the functions of PD-1, in conjunction with the mild, chronic and strain-specific autoimmune phenotypes of PD-1-deficient mice, in contrast to the devastati...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni.2762
更新日期：2013-12-01 00:00:00
abstract：:Transcription factors of the NF-kappaB family are essential regulators of the inflammatory and immune responses. The main 'switch' in NF-kappaB activation is cytoplasmic and leads to the release of NF-kappaB proteins from IkappaB molecules, specific inhibitors that prevent their nuclear accumulation. However, it is be...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni1196
更新日期：2005-05-01 00:00:00
abstract：:Invariant natural killer T cells (iNKT cells) are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled gene expression in iNKT cells during ontogeny and in peripheral subsets as part of the Immunological Genome Project. High-resolution co...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2490
更新日期：2013-01-01 00:00:00
abstract：:Autoimmune diseases are caused by self-reactive lymphocytes that have escaped deletion. Here we have determined the structure of the trimolecular complex for a T cell receptor (TCR) from a patient with multiple sclerosis that causes autoimmunity in transgenic mice. The structure showed a TCR topology notably different...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1187
更新日期：2005-05-01 00:00:00
abstract：:CRACM1 (also called Orai1) constitutes the pore subunit of store-operated calcium release-activated calcium channels. A point mutation in the gene encoding CRACM1 is associated with severe combined immunodeficiency disease in humans. Here we generated CRACM1-deficient mice in which beta-galactosidase activity 'reporte...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1550
更新日期：2008-01-01 00:00:00
abstract：:The autoimmune regulator Aire is expressed in a small proportion of medullary thymic epithelial cells (mTECs) and is crucial in the induction of central T cell tolerance. The origin and development of Aire(+) mTECs, however, are not well understood. Here we demonstrate that the tight-junction components claudin-3 and ...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1438
更新日期：2007-03-01 00:00:00
abstract：:The immunopathogenesis of rheumatoid arthritis (RA) spans decades, beginning with the production of autoantibodies against post-translationally modified proteins (checkpoint 1). After years of asymptomatic autoimmunity and progressive immune system remodeling, tissue tolerance erodes and joint inflammation ensues as t...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/s41590-020-00816-x
更新日期：2021-01-01 00:00:00
abstract：:The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), tha...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-020-0698-1
更新日期：2020-07-01 00:00:00
abstract：:Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1β (IL-1β) as an antiviral host response, and deregulation of the pathways involved can promote inflammatory disease. Here we report a direct cytosolic interaction between the DNA-damage sensor Rad50 and the innate immune system adapto...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2888
更新日期：2014-06-01 00:00:00
abstract：:T lymphocytes and B lymphocytes integrate activating signals to control the size of their proliferative response. Here we report that such control was achieved by timed changes in the production rate of cell-cycle-regulating proto-oncoprotein Myc, with division cessation occurring when Myc levels fell below a critical...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3598
更新日期：2017-01-01 00:00:00
abstract：:Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune syste...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni1519
更新日期：2007-11-01 00:00:00
abstract：:Mycobacterium tuberculosis PtpA, a secreted tyrosine phosphatase essential for tuberculosis pathogenicity, could be an ideal target for a drug against tuberculosis, but its active-site inhibitors lack selectivity over human phosphatases. Here we found that PtpA suppressed innate immunity dependent on pathways of the k...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3096
更新日期：2015-03-01 00:00:00
abstract：:An important function of receptors that signal through immunoreceptor tyrosine-based activation motifs (ITAMs) is to regulate signaling by heterologous receptors. This review describes mechanisms by which ITAM-associated receptors modulate signaling by Toll-like receptors (TLRs), tumor necrosis factor receptor family ...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni.1706
更新日期：2009-04-01 00:00:00
abstract：:The orphan nuclear receptor SHP (small heterodimer partner) is a transcriptional corepressor that regulates hepatic metabolic pathways. Here we identified a role for SHP as an intrinsic negative regulator of Toll-like receptor (TLR)-triggered inflammatory responses. SHP-deficient mice were more susceptible to endotoxi...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2064
更新日期：2011-07-03 00:00:00
abstract：:While a number of extrinsic factors are known to promote the survival of plasma cells (PCs), the signaling intermediates involved remain poorly characterized. Here we identified inducible nitric oxide synthase (iNOS) as an intermediate that supported the survival of PCs. PCs deficient in iNOS (Nos2(-/-) PCs) showed en...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2806
更新日期：2014-03-01 00:00:00
abstract：:The mouse protein Qa-1 (HLA-E in humans) is essential for immunological protection and immune regulation. Although Qa-1 has been linked to CD8 T cell-dependent suppression, the physiological relevance of this observation is unclear. We generated mice deficient in Qa-1 to develop an understanding of this process. Qa-1-...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1063
更新日期：2004-05-01 00:00:00
abstract：:Toll-like receptor 2 (TLR2) initiates inflammation in response to bacterial lipopeptide (BLP). However, the molecular mechanisms enabling the detection of BLP by TLR2 are unknown. Here we investigated the interaction of BLP with human serum proteins and identified vitronectin as a BLP-recognition molecule. Vitronectin...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.1618
更新日期：2008-07-01 00:00:00
abstract：:Cell fate 'decisions' involving multipotential progenitors seem to be 'dictated' by threshold activities of lineage-determining transcription factors. Such 'decisions' are now shown to be reinforced by the induction of secondary transcription factors that act in concert with the primary regulators. ...
journal_title：Nature immunology
pub_type： 评论,新闻
doi：10.1038/ni0207-119
更新日期：2007-02-01 00:00:00
abstract：:Members of the Toll-like receptor (TLR) family are key regulators of both innate and adaptive immune responses. The function of TLRs in various human diseases has been investigated by comparison of the incidence of disease among people having different polymorphisms in genes that participate in TLR signaling. These st...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni1116
更新日期：2004-10-01 00:00:00
abstract：:Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8+ T cell fates, but the observation of equivalent expression of TFs among differentially fated precursor cells suggests additional underlying mechanisms. Here we profiled the genome-wide histone modification...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3706
更新日期：2017-05-01 00:00:00
