Featured
-
-
Article |
Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome
Dietary fibre is metabolized into short-chain fatty acids by gut bacteria. Here the authors show that these metabolites activate the NLRP3 inflammasome in gut epithelial cells and protect mice from injury-induced colitis, suggesting a mechanism for the benefits of a high-fibre diet.
- Laurence Macia
- , Jian Tan
- & Charles R. Mackay
-
Article |
Glycopeptide analogues of PSGL-1 inhibit P-selectin in vitro and in vivo
Inhibiting the interaction between the membrane protein P-selectin and its ligand PSGL-1 is thought to block inflammation. Here the authors report an efficient stereoselective synthesis for PSGL-1 glycopeptide mimics and show that these compounds inhibit PSGL-1/P-selectin in vitro and in vivo.
- Venkata R. Krishnamurthy
- , Mohammed Y. R. Sardar
- & Elliot L. Chaikof
-
Article
| Open AccessXanthine oxidoreductase regulates macrophage IL1β secretion upon NLRP3 inflammasome activation
Activation of NLRP3 inflammasome requires generation of reactive oxygen species. Here the authors show that microbial or tissue damage-derived signals activate xanthine oxidase, which serves as a critical source of reactive oxygen species for inflammasome activation in macrophages.
- Annette Ives
- , Johji Nomura
- & Alexander So
-
Article |
Vimentin regulates activation of the NLRP3 inflammasome
The mechanism of NLRP3 activation remains incompletely characterized. Here the authors show that it is dependent on vimentin, and that NLRP3-mediated lung injury and fibrosis induced by endotoxin, asbestos or bleomycin are reduced in vimentin-deficient mice.
- Gimena dos Santos
- , Micah R. Rogel
- & Karen M. Ridge
-
Article
| Open AccessRIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL
RIPK3 can cause necroptotic cell death via MLKL phosphorylation, and activate NLRP3 inflammasome. Here the authors show that MLKL is dispensable for NLRP3 activation by RIPK3, and highlight how different IAP proteins limit RIPK3 induced apoptosis, necroptosis and IL-1 secretion.
- Kate E. Lawlor
- , Nufail Khan
- & James E. Vince
-
Article |
Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation
Hyperinflammation in cystic fibrosis has been linked to decreased levels of caveolin-1, resulting in higher LPS responsiveness of TLR4. Here the authors show that in a mouse model of cystic fibrosis decreased Akt results in accumulation of miR-199a-5p directly targeting caveolin-1 in macrophages.
- Ping-xia Zhang
- , Jijun Cheng
- & Emanuela M. Bruscia
-
Article
| Open AccessSmall heterodimer partner interacts with NLRP3 and negatively regulates activation of the NLRP3 inflammasome
Excessive NLRP3 inflammasome activation underlies inflammatory diseases such as gout. Here the authors show that orphan nuclear receptor small heterodimer partner protein (SHP) negatively regulates NLRP3, and its loss leads to accumulation of damaged mitochondria and gout-like immunopathology.
- Chul-Su Yang
- , Jwa-Jin Kim
- & Eun-Kyeong Jo
-
Article
| Open AccessRegulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation
T cells that are activated by self-antigens in the periphery can migrate into the brain causing neuroinflammatory disease. Here the authors show that TBK1 is necessary for activated T-cell egress from the lymph node, and blocking TBK1 ameliorates autoimmunity in a mouse model of multiple sclerosis.
- Jiayi Yu
- , Xiaofei Zhou
- & Shao-Cong Sun
-
Article
| Open AccessGlucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M
Glucocorticoids strongly suppress inflammation. Here the authors show that this suppression is mediated by induction of the negative inflammatory regulator IRAK-M, and demonstrate its important role in host defense against the pneumonia-causative bacterium, non-typeable Haemophilus influenzae.
- Masanori Miyata
- , Ji-Yun Lee
- & Jian-Dong Li
-
Article
| Open AccessInnate sensing of microbial products promotes wound-induced skin cancer
Inflammation and wounding can promote cancer development, but the underlying mechanisms are unclear. Here Hoste et al.show that leukocytes sensing flagellin, a component of bacteria, play a key role in inducing skin cancer in the context of wounding and chronic inflammation.
- Esther Hoste
- , Esther N. Arwert
- & Fiona M. Watt
-
Article
| Open AccessInsulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice
Fsp27 mediates ‘fusion’ of lipid droplets in mouse adipose tissue. Here, the authors investigate the physiological consequences of loss of Fsp27 in three different mouse models of ‘energetic overload’, and observe hepatic steatosis and insulin resistance but reduced adipose tissue inflammation.
- Linkang Zhou
- , Shi-Young Park
- & Peng Li
-
Article |
Proinflammatory TLR signalling is regulated by a TRAF2-dependent proteolysis mechanism in macrophages
Activation of Toll-like receptors induces inflammation, which is critical for defence against infection but can cause autoimmunity, and thus needs tight regulation. Here, the authors show that TRAF2 limits inflammatory responses downstream of these receptors by inducing degradation of IRF5 and c-Rel.
- Jin Jin
- , Yichuan Xiao
- & Shao-Cong Sun
-
Article |
STAT3 restrains RANK- and TLR4-mediated signalling by suppressing expression of the E2 ubiquitin-conjugating enzyme Ubc13
The transcription factor STAT3 regulates production of inflammatory cytokines by modulating NF-κB signalling. Here the authors show that STAT3 is a transcriptional repressor of the E2 ubiquitin-conjugating enzyme Ubc13, modulating NF-κB by regulating Ubc13 abundance.
- Huiyuan Zhang
- , Hongbo Hu
- & Stephanie S. Watowich
-
Article
| Open AccessRapid detection of single bacteria in unprocessed blood using Integrated Comprehensive Droplet Digital Detection
Early detection of blood stream infections is essential for providing effective treatments. Here the authors present a system integrating DNAzyme sensors, droplet microfluidics and a high-throughput 3D particle counter that can detect specific, single bacterial cells in blood within a few hours.
- Dong-Ku Kang
- , M. Monsur Ali
- & Weian Zhao
-
Article |
The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors
Genes encoding two pore-forming toxins (γ-haemolysins HlgAB and HlgCB) are present in almost all human Staphylococcus aureus isolates. Here Spaan et al.show that HlgAB and HlgCB target different phagocyte types by interacting with specific chemokine receptors and complement receptors, respectively.
- András N. Spaan
- , Manouk Vrieling
- & Thomas Henry
-
Article
| Open AccessmiR-24 limits aortic vascular inflammation and murine abdominal aneurysm development
Abdominal aortic aneurysm (AAA) is a potentially fatal and often asymptomatic disease whose causes remain unclear. Here the authors show that a microRNA, miR-24, and its target, the glycoprotein chitinase 3-like 1, represent key regulators of AAA development.
- Lars Maegdefessel
- , Joshua M. Spin
- & Philip S. Tsao
-
Article |
Inflammation-driven carcinogenesis is mediated through STING
Chronic inflammation is known to promote tumorigenesis, but the mechanisms underlying this are incompletely understood. Here, the authors show that several carcinogens induce DNA leakage into the cytoplasm, which activates STING-dependent cytokine production and inflammation-driven tumorigenesis.
- Jeonghyun Ahn
- , Tianli Xia
- & Glen N. Barber
-
Article |
IKKα negatively regulates ASC-dependent inflammasome activation
The molecular mechanisms mediating inflammasome activation are not fully elucidated. Here the authors show that the kinase IKKα interacts in the nucleus and perinuclear area with the adaptor molecule ASC, negatively regulating inflammasome activation.
- Bradley N. Martin
- , Chenhui Wang
- & Xiaoxia Li
-
Article |
Circadian rhythm reprogramming during lung inflammation
Whether circadian rhythms occur in settings where clock gene expression is suppressed, such as systemic inflammation, is unclear. Here, the authors examine gene expression and metabolites in the lungs of endotoxemic mice and show that inflammation causes changes in circadian rhythms at the cellular and molecular level.
- Jeffrey A. Haspel
- , Sukrutha Chettimada
- & Augustine M.K. Choi
-
Article |
Negative regulation of NF-κB activity by brain-specific TRIpartite Motif protein 9
ß-TrCP is an adaptor protein that controls activity of several key regulatory proteins including NFκB by ubiquitin-mediated proteolysis. Here Shi et al. demonstrate that ß-TrCP is negatively regulated by the brain-specific protein TRIM9, limiting activation of NFκB and production of proinflammatory cytokines.
- Mude Shi
- , Hyelim Cho
- & Jae U. Jung
-
Article |
IL-37 protects against obesity-induced inflammation and insulin resistance
Inflammation is a hallmark of obesity and driver of various associated pathologies. Here the authors show that mice overexpressing the anti-inflammatory cytokine IL-37 are protected from the metabolic consequences of a high-fat diet, and that plasma levels of IL-37 correlate with insulin sensitivity in humans.
- Dov B. Ballak
- , Janna A. van Diepen
- & Rinke Stienstra
-
Article |
Microfluidic platform for the quantitative analysis of leukocyte migration signatures
Current leukocyte migration assays usually report bulk attractive behaviour of cells within a chemokine gradient. Here, the authors develop a microfluidic device to simultaneously measure several migration responses on exposure to commonly used leukocyte chemokines, and report previously unrecognized cell behaviour.
- Leo Boneschansker
- , Jun Yan
- & Daniel Irimia
-
Article |
Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer
Abundance of certain gut enterobacteria is correlated with inflammation and cancer development in humans, but the interplay between the three factors is unclear. Here the authors show that gut inflammation is required for bacteria-associated tumour development in mouse models.
- Janelle C. Arthur
- , Raad Z. Gharaibeh
- & Christian Jobin
-
Article |
Loss of PIKfyve in platelets causes a lysosomal disease leading to inflammation and thrombosis in mice
PIKfyve is a lipid kinase essential for regulation of membrane homeostasis and vesicle trafficking along the endosomal-lysosomal pathway. Here the authors show that mice lacking PIKfyve exclusively in their platelets exhibit a systemic disorder characterized by multi-organ inflammation and thrombosis due to aberrant platelet lysosome function.
- Sang H. Min
- , Aae Suzuki
- & Charles S. Abrams
-
Article |
Aryl hydrocarbon receptor negatively regulates NLRP3 inflammasome activity by inhibiting NLRP3 transcription
Aryl hydrocarbon receptor is best known as an inducer of detoxification enzymes in response to xenobiotics, but is also increasingly recognized as a negative regulator of immune responses. Here the authors show that it inhibits transcription of a key component of the inflammasome, a sensor of cellular infection-associated stress.
- Wanwan Huai
- , Rui Zhao
- & Wei Zhao
-
Article
| Open AccessRasGRP3 limits Toll-like receptor-triggered inflammatory response in macrophages by activating Rap1 small GTPase
Toll like receptors (TLRs) couple microbial sensing to initiation of immune responses, which are essential for defense against pathogens but may cause immunopathology when activated excessively. Here the authors show that RasGRP3 sets a threshold of TLR activation to prevent immunopathology.
- Songqing Tang
- , Taoyong Chen
- & Jianli Wang
-
Article |
A micro-sterile inflammation array as an adjuvant for influenza vaccines
There is a need of improved adjuvants for influenza vaccines. Here, the authors describe an adjuvant strategy using micro-fractional laser treatment combined with a topical cream containing a TLR 7 ligand that can enhance the immune response to intradermal vaccination with transient, constrained local inflammation.
- Ji Wang
- , Dilip Shah
- & Mei X. Wu
-
Article |
Rab8a interacts directly with PI3Kγ to modulate TLR4-driven PI3K and mTOR signalling
Dorsal membrane ruffles in macrophages accompany pathogen contact and appear before macropinocytosis and phagocytosis. Here, the authors show that these structures are the sites of the accumulation of Toll-like receptor 4 complexes involved in the signalling cascade activated by bacterial lipopolysaccharide.
- Lin Luo
- , Adam A. Wall
- & Jennifer L. Stow
-
Article |
PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis
The role of metabolic reprogramming in the regulation of innate inflammatory response remains incompletely understood. Here, the authors show that pyruvate kinase M2-mediated aerobic glycolysis contributes to inflammatory response, and that inhibition of this pathway protects mice from lethal endotoxemia and sepsis.
- Liangchun Yang
- , Min Xie
- & Daolin Tang
-
Article
| Open AccessChronic inflammation induces telomere dysfunction and accelerates ageing in mice
Many age-related diseases are associated with chronic inflammation. Here Jurk et al. use a mouse model of chronic, low-grade inflammation to support a model by which such inflammation promotes a vicious cycle of oxidative stress, telomere dysfunction and cell senescence that accelerates the ageing process.
- Diana Jurk
- , Caroline Wilson
- & Thomas von Zglinicki
-
Article |
Ezh2 loss promotes development of myelodysplastic syndrome but attenuates its predisposition to leukaemic transformation
Mutations in the EZH2 gene are found in myelodysplastic syndrome (MDS) and are often accompanied by mutations in RUNX1. Here, the authors develop a mouse model of MDS and show that EZH2loss enhances the RUNX1-mediated MDS pathology.
- Goro Sashida
- , Hironori Harada
- & Atsushi Iwama
-
Article |
Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation
Skin-resident IL-17-producing γδT cells have an important role in skin inflammation but their development and trafficking is not well established. Here, Cai et al. unveil differences in the developmental requirements and functional regulation of two subsets of dermal γδT cells.
- Yihua Cai
- , Feng Xue
- & Jun Yan
-
Article
| Open AccessLong non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes
Long non-coding RNAs (lncRNAs) are important regulators of gene expression. Ilott et al. characterize changes in the expression of lncRNAs and enhancer RNAs during the inflammatory response in human monocytes and show that these RNAs can be involved in the regulation of the innate immunity.
- Nicholas E. Ilott
- , James A. Heward
- & Mark A. Lindsay
-
Article |
Combinatorial flexibility of cytokine function during human T helper cell differentiation
Type I interferons (IFNs) have pleiotropic functions in the immune system. Here, the authors evaluate transcriptional signatures generated by type I IFN under distinct T helper cell differentiation programmes and show that, depending on the cytokine context, IFN-α differentially modulates the global cytokine profile of each T helper subset.
- Maxime Touzot
- , Maximilien Grandclaudon
- & Vassili Soumelis
-
Article |
Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production
Metabolic regulation is emerging as an important component of immune response control and may be implicated in the development of inflammatory diseases. Here, the authors show that inflammatory leukocyte recruitment depends on mitochondrial metabolism in epidermal cells in zebrafish.
- Christopher J. Hall
- , Rachel H. Boyle
- & Philip S. Crosier
-
Article |
Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance
Mice lacking Toll-like receptor 4 (Tlr4) do not develop diet-induced insulin resistance. Here Jia et al.create two tissue-specific Tlr4 knockouts to demonstrate that hepatic Tlr4, but not Tlr4 expressed in myeloid cells, is driving obesity-induced inflammation and insulin resistance.
- Lin Jia
- , Claudia R. Vianna
- & Joel K. Elmquist
-
Article |
IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1
Autoimmune diseases are regulated by the balance between pro- and anti-inflammatory cytokines. Here, the authors show that the transcriptional regulator Blimp1 is induced in inflammatory T helper cells by the cytokines IL-27 and IL-12 to counteract pro-inflammatory IL-23 and promote resolution of tissue inflammation.
- Christina Heinemann
- , Sylvia Heink
- & Thomas Korn
-
Article |
IL-21 induces IL-22 production in CD4+ T cells
The cytokine interleukin-22 maintains the integrity of the colonic epithelium during inflammation. Here, the authors show that IL-21 regulates the production of IL-22 in T cells and this mechanism plays a protective role in a mouse model of colitis.
- Ada Yeste
- , Ivan D. Mascanfroni
- & Francisco J Quintana
-
Article |
Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63
The leukocyte receptor P-selectin translocates from Weibel-Palade bodies to the plasma membrane of activated endothelial cells, and is stabilized by CD63. Pöter et al. show that annexin A8 is required for P-selectin-mediated adhesion by regulating the supply of CD63 to the Weibel-Palade bodies.
- Michaela Poeter
- , Ines Brandherm
- & Ursula Rescher
-
Article |
Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation
T cells that mediate neuroinflammation in EAE, a mouse model of multiple sclerosis, act through their production of cytokines. Here, the authors show that the transcription factor Bhlhe40 regulates the expression of GM-CSF and IL-10 by autoreactive T cells and is crucial for EAE induction.
- Chih-Chung Lin
- , Tara R. Bradstreet
- & Brian T. Edelson
-
Article |
Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production
α-tubulin acetylation is an evolutionarily conserved modification but despite its prevalence, the physiological function of this process remains poorly understood. Here, the authors show that α-tubulin acetylation regulates p38 kinase signalling and expression of the anti-inflammatory cytokine IL-10 in macrophages.
- Bin Wang
- , Yan-Hua Rao
- & Tso-Pang Yao
-
Article |
PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model
PI 3-kinase is a major regulator of inflammatory responses. In this study, the authors show that inhibition of the delta isoform of PI 3-kinase attenuates the release of tumour necrosis factor from microglia as well as the signs and symptoms associated with cerebral stroke in an in vivomouse model.
- Pei Ching Low
- , Silvia Manzanero
- & Frédéric A. Meunier
-
Article
| Open AccessActivation of the NLRP1b inflammasome independently of ASC-mediated caspase-1 autoproteolysis and speck formation
The NLRP1b inflammasome activation may lead to pyroptosis and secretion of the inflammatory cytokines IL-1ß and IL-18 but the mechanisms behind these processes are not fully understood. Here, the authors show that they can occur independently of the inflammasome adaptor ASC and without caspase-1 autoprocessing.
- Nina Van Opdenbosch
- , Prajwal Gurung
- & Mohamed Lamkanfi
-
Article
| Open AccessTRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
Gram-negative bacterial infections can often cause inflammation and pain. Meseguer et al. show that the inflammation and pain result from the direct activation of nociceptor TRPA1 channels by lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria.
- Victor Meseguer
- , Yeranddy A. Alpizar
- & Félix Viana
-
Article |
Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway
Inflammasome activation can lead to chronic inflammatory conditions; however, the mechanisms controlling the duration of this activation are not well understood. Here, Ouyang et al.report that adenosine sustains inflammasome activity, which brings insights into the pathology of chronic inflammatory diseases.
- Xinshou Ouyang
- , Ayaz Ghani
- & Wajahat Zafar Mehal
-
Article |
The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis
Gene expression in the vascular endothelium is sensitive to shear forces exerted by the circulation. Here the authors identify miR-712 as a mechanosensitive microRNA expressed in endothelial cells and show that miR-712 inhibits pro-atherogenic processes by downregulating tissue inhibitor of metalloproteinase 3.
- Dong Ju Son
- , Sandeep Kumar
- & Hanjoong Jo
-
Article |
The TSC-mTOR pathway regulates macrophage polarization
Distinct macrophage phenotypes are associated with their polarization to a proinflammatory or alternative state, but it is not well understood how metabolic status affects this process. Here, Byles et al.demonstrate that the mTOR metabolic pathway regulates macrophage differentiation.
- Vanessa Byles
- , Anthony J. Covarrubias
- & Tiffany Horng
-
Article |
Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation
Allergic airway inflammation in asthma can be treated with corticosteroids, but some patients remain unresponsive to this therapy. Here, Kabata et al. show that thymic stromal lymphopoietin contributes to the corticosteroid resistance during airway inflammation through its action on natural helper cells.
- Hiroki Kabata
- , Kazuyo Moro
- & Koichiro Asano
-
Article |
Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway
Sepsis in patients is often accompanied by thrombocytopenia, but the exact role of platelets in the pathogenesis of septicaemia has not been elucidated. Here, Xiang et al. present evidence that platelets may act as anti-inflammatory cells and protect from septic shock.
- Binggang Xiang
- , Guoying Zhang
- & Zhenyu Li