Inflammatory diseases articles within Nature Communications

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• Article
  28 October 2015 | Open Access

  Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes

  Human monocytes exhibit an unconventional one-step pathway of inflammasome activation and IL-1 release in response to LPS. Here the authors show that it is mediated by caspases 4 and 5, and characterize caspase 5 cleavage, Syk and calcium signalling as key mediators of this pathway.

  • Elena Viganò
  • , Catherine Emma Diamond
  •  & Alessandra Mortellaro

• Article
  18 September 2015 | Open Access

  Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling

  RIPK3-mediated signalling regulates the induction of necroptosis and inflammation. Here the authors show that RIPK3-PGAM5-Drp1 pathway is crucial for NKT cell activation independently of cell death in mouse models of melanoma and acute inflammatory liver injury.

  • Young Jun Kang
  • , Bo-Ram Bang
  •  & Motoyuki Otsuka

• Article
  16 September 2015 | Open Access

  Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3β-C/EBPβ pathway

  The endothelial secreted protein Del-1 plays a role in limiting inflammation, and its deficiency is associated with pathology in periodontitis and multiple sclerosis. Here the authors show that the negative regulation of Del-1 by IL-17 involves targeting the transcription factor C/EBPß in a GSK-3ß- dependent manner.

  • Tomoki Maekawa
  • , Kavita Hosur
  •  & George Hajishengallis

• Article
  14 September 2015 | Open Access

  Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation

  IL-33, released by epithelial cells in response to stress, is a potent activator of inflammation. Here Cohenet al. show that secreted IL-33 is rapidly inactivated by disulfide bond formation that prevents binding to its receptor, and that IL-33-related cytokines are susceptible to similar oxidation.

  • E. Suzanne Cohen
  • , Ian C. Scott
  •  & Tomas Mustelin

• Article
  04 August 2015 | Open Access

  Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model

  Environmental enteropathy is a disorder of the small intestine that contributes to the persistence of childhood malnutrition worldwide. Here, Brownet al. show in mice that early-life malnourishment, in combination with exposure to commensal bacteria, remodels the small intestine to resemble features of the disease.

  • Eric M. Brown
  • , Marta Wlodarska
  •  & B. Brett Finlay

• Article
  21 July 2015 | Open Access

  Phosphorylation status determines the opposing functions of Smad2/Smad3 as STAT3 cofactors in T_H17 differentiation

  TGF-ß and IL-6 are the essential cytokines for mediating the differentiation of IL-17-producing CD4+ T helper cells (T_H17). Here, Yoon et al. provide more insights into this process and describe the opposing roles of TGFß-signalling intermediates Smad2 and Smad3 as STAT3 cofactors in Th17 differentiation.

  • Jeong-Hwan Yoon
  • , Katsuko Sudo
  •  & Mizuko Mamura

• Article | 15 July 2015

  Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

  Adiponectin levels are decreased in metabolic syndrome and psoriasis patients. Here the authors show that adiponectin suppresses the pathogenic production of IL-17 of γδ T cells, and adiponectin administration improves psoriasis-like symptoms in a mouse model of the disease.

  • Sayaka Shibata
  • , Yayoi Tada
  •  & Shinichi Sato

• Article | 13 July 2015

  Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation

  Syndecan-4 is a surface protein implicated in the regulation of cytoskeleton, adhesion and migration. Here the authors show that blocking syndecan-4 prevents dendritic cell migration into the lung and inhibits the development of allergic airway inflammation in mice.

  • Tobias Polte
  • , Susanne Petzold
  •  & Marco Averbeck

• Article | 10 July 2015

  PGD₂ deficiency exacerbates food antigen-induced mast cell hyperplasia

  Mast cells are major contributors to allergy. Here the authors show that prostaglandin D2-deficient mast cells produce more chemoattractants, promoting mast cell hyperplasia and exacerbating allergic responses in a mouse model of food allergy.

  • Tatsuro Nakamura
  • , Shingo Maeda
  •  & Takahisa Murata

• Article
  03 July 2015 | Open Access

  NF-κB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis

  Psoriasis is accompanied by NF-κB activation and hyperplasia. Here the authors show that NF-κB transcriptionally activates miR-31, which downregulates a negative cell cycle regulator protein phosphatase 6, and that this is critical for NF-κB to drive keratinocyte hyperproliferation.

  • Sha Yan
  • , Zhenyao Xu
  •  & Honglin Wang

• Article | 23 June 2015

  Aquaporin-3-mediated hydrogen peroxide transport is required for NF-κB signalling in keratinocytes and development of psoriasis

  Aquaporin-3 (AQP3) mediates cellular uptake of water and hydrogen peroxide (H₂O₂). Here, the authors show that TNF-induced H₂O₂enters keratinocytes via AQP3, eliciting NF-κB activation and the development of psoriasis, and identify AQP3 as a potential therapeutic target for this inflammatory immune-mediated disease.

  • Mariko Hara-Chikuma
  • , Hiroki Satooka
  •  & A. S. Verkman

• Article | 23 June 2015

  Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites

  Growing evidence suggests that environmental rather than genetic factors are major contributors to asthma development. Here the authors show that high intake of dietary fibre by pregnant mice increases resistance of their progeny to the development of allergic airways disease.

  • Alison N. Thorburn
  • , Craig I. McKenzie
  •  & Charles R. Mackay

• Article | 13 April 2015

  A fungal protease allergen provokes airway hyper-responsiveness in asthma

  Airway hyper-responsiveness, a hallmark of asthma, is often associated with sensitization to fungi. Here, the authors show that a fungal protease allergen Asp f13/Alp1 from Aspergillus fumigatuscan promote airway hyper-responsiveness in asthma via its effect on the airway smooth muscle cells.

  • Nariman A. Balenga
  • , Michael Klichinsky
  •  & Kirk M. Druey

• Article
  09 April 2015 | Open Access

  Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis

  Psoriasis is a chronic inflammatory disease affecting up to 3% of the population. Here, Zuo et al.perform exome array analysis, identify single-nucleotide polymorphisms at 15 new loci, implicating several biological pathways in psoriasis risk and disease heritability.

  • Xianbo Zuo
  • , Liangdan Sun
  •  & Xuejun Zhang

• Article
  02 April 2015 | Open Access

  Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin

  The lipid sphingosine-1-phosphate (S1P) is known to mediate leukocyte recruitment in inflammation. Here, Nussbaum et al.show that S1P, via its receptor S1P3, also regulates leukocyte rolling on endothelium by promoting the presentation of the adhesion molecule P-selectin on the endothelial surface.

  • Claudia Nussbaum
  • , Sarah Bannenberg
  •  & Bodo Levkau

• Article
  18 March 2015 | Open Access

  RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling

  Vascular inflammation plays a key role in pathogenesis of major vascular diseases. Here the authors show that Regulator of G-Protein Signaling-1 (RGS1) controls macrophage function in the development of vascular inflammation that underlies atherosclerosis and abdominal aortic aneurysms in mice and humans.

  • Jyoti Patel
  • , Eileen McNeill
  •  & Keith M. Channon

• Article | 17 March 2015

  A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production

  Receptor Interacting Protein Kinase 2 (RIPK2) mediates innate immune signalling in response to intracellular pathogens, but its aberrant activation contributes to autoimmune pathologies. Here Nachbur et al.describe a RIPK2 inhibitor that is effective in a mouse model of multiple sclerosis.

  • Ueli Nachbur
  • , Che A. Stafford
  •  & John Silke

• Article | 24 February 2015

  Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

  Food allergy is a growing clinical and public health burden. Here, the authors carry out a genome-wide association study in samples with well-defined allergies to a variety of foods, and identify the 6p21.32 region that significantly increases risk of developing peanut allergy.

  • Xiumei Hong
  • , Ke Hao
  •  & Xiaobin Wang

• Article | 18 February 2015

  Dendritic cells induce Th2-mediated airway inflammatory responses to house dust mite via DNA-dependent protein kinase

  House dust mites are a common cause of allergic asthma. Here, the authors show that the Th2-mediated inflammatory responses triggered by mites in mouse airways are mediated by the activation of DNA-dependent protein kinase (DNA-PK) in dendritic cells.

  • Amarjit Mishra
  • , Alexandra L. Brown
  •  & Jay H. Chung

• Article | 17 February 2015

  The polymeric mucin Muc5ac is required for allergic airway hyperreactivity

  Asthma is associated with mucus overproduction; however, the immunological consequences of excess mucus remain poorly understood. Here the authors show that formation of airway plugs by mucus promotes airway hypersensitivity, while deletion of mucous component Muc5acablates it independently of inflammation.

  • Christopher M. Evans
  • , Dorota S. Raclawska
  •  & Burton F. Dickey

• Article
  16 January 2015 | Open Access

  Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma

  Common variants account for only a small amount of the heritable risk for developing asthma. Using a meta-analysis approach, Igartua et al. identify one low-frequency missense mutation and two genes with functional variants that are associated with asthma, but only in specific ethnic groups.

  • Catherine Igartua
  • , Rachel A. Myers
  •  & Carole Ober

• Article
  23 December 2014 | Open Access

  Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation

  Chronic consumption of a Western-type diet leads to systemic inflammation of undefined origin, which contributes to metabolic disease. Here Progatzky et al. identify an immediate early step in the process by showing that dietary cholesterol rapidly activates inflammasomes in the gut epithelium.

  • Fränze Progatzky
  • , Navjyot J. Sangha
  •  & Margaret J. Dallman

• Article | 19 November 2014

  GWAS identifies four novel eosinophilic esophagitis loci

  Eosinophilic oesophagitis (EoE) is an allergic, inflammatory disorder of the oesophagus. Here the authors carry out a genome-wide association study in over 5,000 individuals and identify four genetic loci that affect the onset of EoE.

  • Patrick M. A. Sleiman
  • , Mei-Lun Wang
  •  & Hakon Hakonarson

• Article | 13 November 2014

  Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation

  Epigenetic changes during the differentiation of bone-resorbing cells have important implications in bone remodelling. Here the authors target this pathway with I-BET151, an inhibitor of bromo and extra-terminal proteins that inhibits expression of the MYC-NFAT axis and suppresses bone loss in multiple mouse models.

  • Kyung-Hyun Park-Min
  • , Elisha Lim
  •  & Lionel B Ivashkiv

• Article
  13 November 2014 | Open Access

  Fc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by human M2 macrophages

  M2-polarized macrophages are generally considered anti-inflammatory, but whether polarization markers always reflect functional states remains debatable. Here the authors show that complexed IgG and TLR co-stimulation, observed in infections or rheumatoid arthritis, elicits an inflammatory response in M2 macrophages.

  • Lisa T. C. Vogelpoel
  • , Ivo S. Hansen
  •  & Jeroen den Dunnen

• Article | 30 September 2014

  A20 controls intestinal homeostasis through cell-specific activities

  Aetiology of colitis is highly complex and incompletely understood. Here the authors show in mouse models that A20 deubiquitinase limits pro-inflammatory cytokine production in myeloid cells while inhibiting proapoptotic response to these cytokines in enterocytes, and that only upon losing both functions intestinal pathologies develop.

  • Lars Vereecke
  • , Sara Vieira-Silva
  •  & Geert van Loo

• Article | 01 September 2014

  TSC1 controls macrophage polarization to prevent inflammatory disease

  Macrophages can be polarized to inflammatory M1 and anti-inflammatory M2 phenotypes, depending on the cytokine milieu. Here, Zhu et al.demonstrate that tuberous sclerosis complex 1 (TSC1) inhibits M1 and promotes M2 polarization of macrophages to prevent inflammatory disorders.

  • Linnan Zhu
  • , Tao Yang
  •  & Yong Zhao

• Article | 22 August 2014

  Grail controls Th2 cell development by targeting STAT6 for degradation

  The mechanisms controlling Th2-mediated inflammation are not well defined. Here the authors show that the E3 ubiquitin ligase Grail is involved in a negative feedback loop with Th2-specific transcription factors and regulates Th2-mediated allergic asthma responses.

  • Anupama Sahoo
  • , Andrei Alekseev
  •  & Roza Nurieva

• Article | 07 August 2014

  Nitric oxide enhances Th9 cell differentiation and airway inflammation

  Th9 cells are a subset of T helper cells that protect hosts against helminthic infection, but can also mediate allergic disease through overexpression of the cytokine IL-9. Here, Niedbala et al.show that nitric oxide is a potent enhancer of Th9 differentiation via the activation of p53 protein.

  • Wanda Niedbala
  • , Anne-Gaelle Besnard
  •  & Foo Y. Liew

• Article
  06 August 2014 | Open Access

  Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity

  Alarmins are locally released during inflammation and are early amplifiers of inflammation. Here Vogl et al.show that the alarmin S100A8/S100A9 can be used as a sensitive marker to detect subclinical inflammation and follow disease progression in a variety of disease models.

  • Thomas Vogl
  • , Michel Eisenblätter
  •  & Johannes Roth

• Article
  05 August 2014 | Open Access

  A designer cell-based histamine-specific human allergy profiler

  The advancement of sensitive, accurate and non-invasive methods to identify the allergen that drives allergic disease in an individual remains a challenge. Here, the authors develop a synthetic biology approach using human designer cells to profile allergic reactions against an array of allergens measuring histamine release from whole blood.

  • David Ausländer
  • , Benjamin Eggerschwiler
  •  & Martin Fussenegger

• Article | 09 July 2014

  Sequencing-based approach identified three new susceptibility loci for psoriasis

  Although psoriasis is a chronic disorder affecting approximately 2% of the population, little is known about the underlying genetic architecture. Here, the authors carry out exome sequencing in a large Han Chinese cohort of psoriasis patients and healthy controls, and identify three new genes that may increase risk of developing the disease.

  • Yujun Sheng
  • , Xin Jin
  •  & Xuejun Zhang

• Article | 13 June 2014

  Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

  Acne vulgarisis a common, inflammatory skin disorder. Here the authors carry out a genome-wide association study and identify three genetic variants that associate with an increased risk of developing acne, which together suggest a mechanistic role for the TGFβ cell signalling pathway in acne development and progression.

  • Alexander A. Navarini
  • , Michael A. Simpson
  •  & Jonathan N. Barker

• Article | 07 May 2014

  An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells

  Contact hypersensitivity is caused by the reaction of T cells to various chemical contact allergens. Here, the authors unveil the signalling pathway induced in dendritic cells in response to contact allergens, which is required for the stimulation of T-cell sensitization in contact hypersensitivity.

  • Shinsuke Yasukawa
  • , Yoshiyuki Miyazaki
  •  & Hiromitsu Hara

• Article | 10 April 2014

  Nucleic acid sensing by T cells initiates Th2 cell differentiation

  Nucleic acids modulate T cell responses; however, the physiological significance of this property remains unclear. Here, the authors show that self-DNA complexes with antimicrobial peptides or histones, which mediates T cell costimulation to induce Th2 cell differentiation.

  • Takayuki Imanishi
  • , Chitose Ishihara
  •  & Takashi Saito

• Article | 24 January 2014

  Two potential therapeutic antibodies bind to a peptide segment of membrane-bound IgE in different conformations

  Two antibodies targeting the CεmX domain of membrane-bound IgE on human B lymphocytes are being developed to treat allergy. Here, the authors map the antigenic epitopes of the two antibodies and show that they bind to different conformations of the same peptide region.

  • Hsing-Mao Chu
  • , Jon Wright
  •  & Carmay Lim

• Article | 20 January 2014

  MafB promotes atherosclerosis by inhibiting foam-cell apoptosis

  In the early stages of atherosclerosis, macrophages in the vessel wall convert into foam cells, which promote the rise of atherosclerotic plaques. Here Hamada et al. show that the macrophage transcription factor MafB inhibits foam-cell apoptosis, and that its absence promotes atherosclerosis development in mice.

  • Michito Hamada
  • , Megumi Nakamura
  •  & Satoru Takahashi

• Article | 20 January 2014

  A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

  Inflammatory processes in atherosclerotic lesions promote disease progression and plaque rupture. Here the authors load the drug statin into nanoparticles made of recombinant high-density lipoprotein and show that these accumulate in atherosclerotic plaques and reduce plaque inflammation in mice.

  • Raphaël Duivenvoorden
  • , Jun Tang
  •  & Willem J. M. Mulder

• Article | 07 January 2014

  Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne

  Severe acne is a common skin disease characterized by chronic inflammation and potential scarring. Here, the authors have identified genetic variants at two loci associated with severe acne and provide insight into the genetic architecture and biological pathways underlying the disease.

  • Li He
  • , Wen-Juan Wu
  •  & Ya-Ping Zhang

• Article | 25 October 2013

  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 | 18 October 2013

  Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop

  Autoimmune T cell receptors can interact with both self and microbial antigens, but the structural basis for crossreactivity is not fully understood. Here, the authors provide structural insights into binding characteristics of the autoreactive T cell receptor Hy.1B11 to both self and pathogen-derived peptides.

  • Dhruv K. Sethi
  • , Susana Gordo
  •  & Kai W. Wucherpfennig

• Article | 23 September 2013

  ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48

  ORMDL3has been identified as a gene associated with asthma susceptibility, but its exact role in the pathogenesis of this disease is not well known. Here, the authors propose that induction of ORMDL3 in eosinophils modulates the expression of integrins, which could contribute to a key inflammatory event in asthma.

  • Sung Gil Ha
  • , Xiao Na Ge
  •  & P. Sriramarao

• Article
  17 September 2013 | Open Access

  Genome-wide mapping of gene–microbiota interactions in susceptibility to autoimmune skin blistering

  The pathogenesis of inflammatory disorders afflicting the skin is multifactorial. Srinivas et al. show that diversity of the skin microbiota is a critical factor determining the susceptibility to epidermolysis bullosa acquisita, a chronic mucocutaneous autoimmune skin blistering disease.

  • Girish Srinivas
  • , Steffen Möller
  •  & Saleh M. Ibrahim

• Article | 10 June 2013

  Persistent infection with Crohn’s disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis

  Intestinal infection with adherent-invasive Escherichia coliis associated with Crohn’s disease in humans; however, its functional role remains unclear, in part due to a lack of animal models, which sustain chronic disease. Here the authors establish such a model in mice and show that it shares features with human Crohn’s disease.

  • Cherrie-Lee N. Small
  • , Sarah A. Reid-Yu
  •  & Brian K. Coombes

• Article | 06 June 2012

  Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation

  Inositol polyphosphate 4 phosphatase regulates phosphoinositide signalling and is associated with an increased risk of asthma. Aichet al. show that, in a mouse model of airway inflammation, calpains degrade inositol polyphosphate 4 phosphatase resulting in exacerbated phosphoinositide 3-kinase signalling.

  • Jyotirmoi Aich
  • , Ulaganathan Mabalirajan
  •  & Balaram Ghosh