Featured
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Letter |
Induction of innate immune memory via microRNA targeting of chromatin remodelling factors
The microRNAs miR-221 and miR-222 regulate the reprogramming of macrophages during the development of lipopolysaccharide tolerance, and increased expression of these microRNAs is associated with immunosuppression and poor prognosis in patients with sepsis.
- John J. Seeley
- , Rebecca G. Baker
- & Sankar Ghosh
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Article |
SAMHD1 acts at stalled replication forks to prevent interferon induction
SAMHD1 has an essential role in the replication stress response and prevents inflammation by activating the MRE11 nuclease to degrade nascent DNA strands at stalled replication forks, thus enabling replication.
- Flavie Coquel
- , Maria-Joao Silva
- & Philippe Pasero
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Letter |
Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1
WebTreatment of lipopolysaccharide-activated macrophages with the cell-permeable itaconate derivative 4-octyl itaconate activates the anti-inflammatory transcription factor Nrf2 by alkylating key cysteine residues on the KEAP1 protein.
- Evanna L. Mills
- , Dylan G. Ryan
- & Luke A. O’Neill
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Letter |
Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas
In mouse pancreas cells with only one copy of the Nr5a2 gene, the orphan nuclear receptor NR5A2 undergoes a marked transcriptional shift from differentiation-specific to inflammatory genes, which results in an epithelial-cell-autonomous basal pre-inflammatory state.
- Isidoro Cobo
- , Paola Martinelli
- & Francisco X. Real
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Letter |
Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation
A report of RNA 5-methylcytosine oxidation by mammalian Tet2, showing that Tet2 promotes infection-induced myelopoiesis in mice via a mechanism involving the repression of Socs3 mRNA, a previously unknown regulatory role of Tet2 at the epitranscriptomic level.
- Qicong Shen
- , Qian Zhang
- & Xuetao Cao
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Letter |
Precision editing of the gut microbiota ameliorates colitis
Tungstate inhibits molybdenum-cofactor-dependent microbial respiratory pathways and shows potential as a selective treatment for microbial imbalances that occur during inflammation of the gastrointestinal tract.
- Wenhan Zhu
- , Maria G. Winter
- & Sebastian E. Winter
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Letter |
Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy
A product of the soluble epoxide hydrolase enzyme, 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP), is implicated in the pathogenesis of diabetic retinopathy; levels of 19,20-DHDP increase in the retinas of mice and humans with diabetes, and inhibition of its production can rescue vascular abnormalities in a mouse model of the disease.
- Jiong Hu
- , Sarah Dziumbla
- & Ingrid Fleming
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Article |
Inflammatory memory sensitizes skin epithelial stem cells to tissue damage
After acute inflammation, epithelial stem cells retain a memory that accelerates restoration of the skin barrier during subsequent tissue damage, and this enhancement is dependent on the AIM2 inflammasome and its downstream effectors.
- Shruti Naik
- , Samantha B. Larsen
- & Elaine Fuchs
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Letter |
Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing
Lipolysis declines with age because NLRP3 inflammasome-activated adipose tissue macrophages reduce levels of noradrenaline by upregulating genes that control its degradation, such as GDF3 and MAOA.
- Christina D. Camell
- , Jil Sander
- & Vishwa Deep Dixit
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Review Article |
Inflammation, metaflammation and immunometabolic disorders
The delicate balance between the immune system and metabolism, and its implications for obesity and metabolic disease are explored.
- Gökhan S. Hotamisligil
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Letter |
Feedback control of AHR signalling regulates intestinal immunity
Cytochrome P4501 enzymes have a role in the regulation of aryl hydrocarbon receptor ligand levels in the gut, affecting innate lymphoid and TH17 cell responses.
- Chris Schiering
- , Emma Wincent
- & Brigitta Stockinger
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Letter |
NLRC3 is an inhibitory sensor of PI3K–mTOR pathways in cancer
Mice deficient in the protein NLRC3 are highly prone to colitis and tumour development in the colon as NLRC3 suppresses the activation of mTOR signalling pathways that help drive tumorigenesis.
- Rajendra Karki
- , Si Ming Man
- & Thirumala-Devi Kanneganti
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Letter |
RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation
The enzyme RIPK1 functions through its RHIM domain to prevent ZBP1-mediated activation of RIPK3–MLKL-dependent necroptosis, thus preventing perinatal lethality and skin inflammation in adult mice.
- Juan Lin
- , Snehlata Kumari
- & Manolis Pasparakis
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Letter |
Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation
Macrophage-derived insulin-like growth factor enhances the uptake of microvesicles by non-professional phagocytes, such as airway epithelial cells and fibroblasts, thereby dampening tissue inflammation.
- Claudia Z. Han
- , Ignacio J. Juncadella
- & Kodi S. Ravichandran
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Letter |
PI3Kγ is a molecular switch that controls immune suppression
Modulation of PI3Kγ activity regulates macrophage polarization during inflammation and cancer, whilst combining PI3Kγ inhibition with immune checkpoint inhibitors leads to synergistic tumour-inhibitory effects.
- Megan M. Kaneda
- , Karen S. Messer
- & Judith A. Varner
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Brief Communications Arising |
Does caspase-12 suppress inflammasome activation?
- Lieselotte Vande Walle
- , Daniel Jiménez Fernández
- & Mohamed Lamkanfi
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Letter |
Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection
Genetic engineering in mice reveals that autophagy is not an essential mechanism in myeloid cells for controlling Mycobacterium tuberculosis infection, and that autophagy factor ATG5 protects organisms by regulating neutrophil influx and tissue damage.
- Jacqueline M. Kimmey
- , Jeremy P. Huynh
- & Christina L. Stallings
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Article |
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Gasdermin D is identified as the required substrate for pyroptosis, mediating caspase-11 function in the non-canonical inflammasome pathway; the cleaved N-terminal domain is shown to trigger pyroptosis.
- Nobuhiko Kayagaki
- , Irma B. Stowe
- & Vishva M. Dixit
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Letter |
Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6
The Tet2 enzyme, which catalyses de novo hydroxymethylation of DNA, is shown here to act as a transcriptional repressor by recruiting the histone deacetylase Hdac2 to the Il6 promoter in the course of resolution of the LPS-induced inflammatory response.
- Qian Zhang
- , Kai Zhao
- & Xuetao Cao
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Letter |
Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome
Emulsifying agents, which are common food additives in the human diet, induce low-grade inflammation and obesity/metabolic syndrome in mice, suggesting that further investigation into the potential impact of dietary emulsifiers on the gut microbiota and human heath are warranted.
- Benoit Chassaing
- , Omry Koren
- & Andrew T. Gewirtz
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Letter |
CEACAM1 regulates TIM-3-mediated tolerance and exhaustion
CEACAM1 functions as a novel heterophilic ligand for TIM-3 and is necessary for TIM-3-mediated tolerance, which has marked consequences for inflammation, infection and cancer.
- Yu-Hwa Huang
- , Chen Zhu
- & Richard S. Blumberg
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Letter |
Dendritic cells control fibroblastic reticular network tension and lymph node expansion
During inflammation, the lymph node stromal compartment is shown to accommodate high numbers of infiltrating lymphocytes by relaxing the cytoskeleton of fibroblastic reticular cells, allowing the latter to stretch and the lymph node to expand.
- Sophie E. Acton
- , Aaron J. Farrugia
- & Caetano Reis e Sousa
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Letter |
Dietary modulation of the microbiome affects autoinflammatory disease
Pstpip2-mutant mice fed a high-fat diet are protected against inflammatory bone disease and bone erosion; this protection is associated with reductions in intestinal Prevotella levels and pro-IL-1β expression, and is dependent on the deletion of both caspases 1 and 8.
- John R. Lukens
- , Prajwal Gurung
- & Thirumala-Devi Kanneganti
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Article |
Inflammatory caspases are innate immune receptors for intracellular LPS
Caspase-4 and caspase-11 are shown to be the direct sensors for cytoplasmic lipopolysaccharide in humans and mice, respectively, mediating inflammatory cell death in intracellular bacterial infection.
- Jianjin Shi
- , Yue Zhao
- & Feng Shao
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Review Article |
Nucleotide signalling during inflammation
Extracellular ATP released from cells during inflammatory responses predominantly functions as a signalling molecule through the activation of purinergic P2 receptors and contributes to both beneficial and detrimental inflammatory responses; this review examines P2 receptor signalling via ATP and its effect on the outcome of inflammatory and infectious diseases.
- Marco Idzko
- , Davide Ferrari
- & Holger K. Eltzschig
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Letter |
Protective mucosal immunity mediated by epithelial CD1d and IL-10
Here, the presentation of lipid antigens by CD1d is shown to induce retrograde anti-inflammatory signalling in intestinal epithelial cells, resulting in the production of IL-10.
- Torsten Olszak
- , Joana F. Neves
- & Richard S. Blumberg
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Letter |
Endosomes are specialized platforms for bacterial sensing and NOD2 signalling
The endo-lysosomal transporters SLC15A3 and SLC15A4 provide a portal of entry for extracellular bacterial products that activate the cytoplasmic sensor NOD2; these results establish the importance of endosomes as signalling platforms specialized for triggering innate immune responses.
- Norihiro Nakamura
- , Jennie R. Lill
- & Ira Mellman
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Article |
Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection
Quiescent CD4 T cells in lymphoid tissues are shown to die after HIV-1 infection by caspase-1-mediated pyroptosis, a highly inflammatory form of programmed cell death; caspase 1 inhibitors, which are safe for human use, can rescue the cell death in vitro raising the possibility of new therapeutics targeting the host instead of the virus.
- Gilad Doitsh
- , Nicole L. K. Galloway
- & Warner C. Greene
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Outlook |
Inflammation: A complex problem
Multi-protein inflammasomes are being implicated in a surprising number of diseases, and researchers are keen to find out why.
- Katharine Gammon
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Letter |
cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING
Cytosolic DNA induces type I interferon via activation of STING; the immediate STING activator is produced by the recently identified DNA sensor cGAS and is shown here to be an unorthodox cyclic dinucleotide harbouring a 2′-5′ linkage between guanosine and adenosine.
- Andrea Ablasser
- , Marion Goldeck
- & Veit Hornung
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Letter |
RIP1-driven autoinflammation targets IL-1α independently of inflammasomes and RIP3
This study defines a novel RIP1-kinase- and IL-1α-dependent autoinflammatory pathway that depends on NF-κB and is controlled by the tyrosine phosphatase SHP-1.
- John R. Lukens
- , Peter Vogel
- & Thirumala-Devi Kanneganti
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Letter |
Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo
Two-photon intravital imaging is used here to define the regulation of interstitial neutrophil migration at local sites of cell death upon sterile tissue injury and infection; leukotriene B4 (LTB4) is shown to act between neutrophils as a signal relay molecule that acts to enhance the radius of neutrophil recruitment within the inflamed interstitium, and also to control, in concert with integrin receptors, dense neutrophil clustering for tight wound seal formation.
- Tim Lämmermann
- , Philippe V. Afonso
- & Ronald N. Germain
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Letter |
Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria
Group 3 innate lymphoid cells are shown to process and present antigen and to control CD4+ T-cell responses to intestinal commensal bacteria through an MHC-class-II-dependent mechanism.
- Matthew R. Hepworth
- , Laurel A. Monticelli
- & Gregory F. Sonnenberg
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Outlook |
Perspective: Don't be superficial
Severe psoriasis carries cardiovascular risks. Dermatologists should consider more than just patients' outer layers, argues Henning Boehncke.
- Wolf-Henning Boehncke
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Outlook |
Immunology: A many layered thing
No mere passive barrier, the skin is being revealed to be an active part of the immune system. Researchers are now starting to understand its role in driving psoriasis.
- Claire Ainsworth
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Letter |
NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Alzheimer’s-prone mice deficient in NLRP3 or caspase-1 fail to develop learning deficits and show reduced neuropathology.
- Michael T. Heneka
- , Markus P. Kummer
- & Douglas T. Golenbock
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Letter |
Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin
Chronic inflammation is a feature of the ageing brain and some neurodegenerative diseases; the authors show that astrocytes normally suppress neuroinflammation through activation of their DRD2 receptor by CRYAB, potentially opening new avenues for treatments.
- Wei Shao
- , Shu-zhen Zhang
- & Jia-wei Zhou
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Letter |
Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation
Airway epithelial cells are important in immune homeostasis in that they dampen immune activation by clearing dying cells and producing anti-inflammatory cytokines.
- Ignacio J. Juncadella
- , Alexandra Kadl
- & Kodi S. Ravichandran
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Letter |
The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP
Evidence is presented that activation of the NLRP3 inflammasome is regulated by the calcium-sensing receptor (CASR).
- Geun-Shik Lee
- , Naeha Subramanian
- & Jae Jin Chae
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Research Highlights |
Immune response spurs cell switch
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Letter |
Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth
In a mouse model of colorectal cancer, barrier deterioration results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives IL-23-dependent tumour growth.
- Sergei I. Grivennikov
- , Kepeng Wang
- & Michael Karin
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Letter |
IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine
IL-22 is one of the factors that, although important for wound healing, also promote tumorigenesis; the regulation of IL-22BP, the IL-22 binding protein, via the NLRP3 and NLRP6 inflammasomes provides an unanticipated mechanism, controlling IL-22 and thereby the development of colon cancer.
- Samuel Huber
- , Nicola Gagliani
- & Richard A. Flavell
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Research Highlights |
Fatty plaque link to inflammation
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Outlook |
Health impact: Breathless
COPD is one of the world's biggest killers, but awareness is low, diagnosis is often missed, and in many countries the extent of the problem is not even well-documented.
- Amber Dance
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Outlook |
Perspective: Clues, not conclusions
Scientists have some way to go before they can prove that COPD should be treated as an autoimmune disease, says Steven R. Duncan.
- Steven R. Duncan
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Letter |
Rapid induction of inflammatory lipid mediators by the inflammasome in vivo
Induction of an eicosanoid storm is shown to be an unexpected consequence of inflammasome activation in peritoneal macrophages, leading to vascular leakage and rapid death in mice.
- Jakob von Moltke
- , Norver J. Trinidad
- & Russell E. Vance
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Letter |
Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1
Activation of the non-canonical, pro-inflammatory caspase-11 by Salmonella typhimurium is shown to contribute to bacterial spread and pathogenesis by the induction of macrophage cell death.
- Petr Broz
- , Thomas Ruby
- & Denise M. Monack
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Letter |
ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation
Mutations in angiotensin-converting enzyme 2 are shown to predispose mice to colitis as a consequence of neutral amino acid malabsorption and a change in the resident microbiota; these results could explain how protein malnutrition — affecting up to one billion people — leads to intestinal inflammation.
- Tatsuo Hashimoto
- , Thomas Perlot
- & Josef M. Penninger
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News & Views |
Bad matters made worse
Heart attacks occur when lipoprotein-driven inflammation called atherosclerosis triggers blood clotting in the arteries. It seems that the attacks can, in turn, accelerate atherosclerosis by fanning the inflammation. See Letter p.325
- Ira Tabas