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Article
| Open Access
IL-10 constrains sphingolipid metabolism to limit inflammation
IL-10 exerts its anti-inflammatory activity in macrophages by increasing the expression of enzymes that promote fatty acid desaturation and downstream regulation of the transcription factor REL.
- Autumn G. York
- , Mathias H. Skadow
- & Richard A. Flavell
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Review Article |
A break in mitochondrial endosymbiosis as a basis for inflammatory diseases
We suggest that as mitochondrial signals probably contribute to the homeostatic role of inflammation, dysregulation of these processes may lead to autoimmune and inflammatory diseases, with increasing evidence pointing to the recent failure of endosymbiosis being crucial.
- Michael P. Murphy
- & Luke A. J. O’Neill
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Article |
Epithelial IFNγ signalling and compartmentalized antigen presentation orchestrate gut immunity
IFNγ signalling in epithelial cells promotes antigen presentation that confers intra-epithelial T cells the ability to limit extracellular ATP and consequent NLRP3 inflammasome activation, controlling pathogenic transformation of CD4+ T cells that promotes colitis and colorectal cancer in mouse models.
- Ankit Malik
- , Deepika Sharma
- & Bana Jabri
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Article
| Open Access
Non-cell-autonomous cancer progression from chromosomal instability
Chromosomal instability in cancer is linked to endoplasmic reticulum stress signalling, immune suppression and metastasis, which is mediated by the cGAS–STING pathway, suppression of which can reduce metastasis.
- Jun Li
- , Melissa J. Hubisz
- & Samuel F. Bakhoum
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Article |
Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice
Mice overexpressing Has2 from the naked mole-rat showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, attenuated inflammation through several pathways, extended lifespan and improved healthspan.
- Zhihui Zhang
- , Xiao Tian
- & Vera Gorbunova
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Article |
Autoimmunity in Down’s syndrome via cytokines, CD4 T cells and CD11c+ B cells
An autoimmune-prone state of steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation contributes to a breach in immune tolerance in individuals with Down’s syndrome.
- Louise Malle
- , Roosheel S. Patel
- & Dusan Bogunovic
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Article |
ADAR1 mutation causes ZBP1-dependent immunopathology
The autoinflammatory pathology associated with alteration of the ZBD domain of the RNA-editing enzyme ADAR1 is driven by signalling that is dependent on the nucleotide sensor ZBP1.
- Nicholas W. Hubbard
- , Joshua M. Ames
- & Andrew Oberst
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Article |
Within-host evolution of a gut pathobiont facilitates liver translocation
Within-host evolution is a critical regulator of commensal pathogenicity that provides a unique source of stochasticity in the development and progression of microbiota-driven disease.
- Yi Yang
- , Mytien Nguyen
- & Noah W. Palm
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Article |
Inflammasome activation in infected macrophages drives COVID-19 pathology
A new humanized mouse model for COVID-19 demonstrates SARS-CoV-2 infection and subsequent activation of inflammasomes in human macrophages as a critical driver of disease.
- Esen Sefik
- , Rihao Qu
- & Richard A. Flavell
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Article |
Neuroimmune cardiovascular interfaces control atherosclerosis
The peripheral nervous system uses neuroimmune cardiovascular interfaces to assemble a structural artery–brain circuit, and therapeutic intervention in the artery–brain circuit attenuates atherosclerosis.
- Sarajo K. Mohanta
- , Li Peng
- & Andreas J. R. Habenicht
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Article |
CAR directs T cell adaptation to bile acids in the small intestine
Activation of the nuclear hormone receptor CAR in T cells protects the small intestine against bile acid-driven inflammation.
- Mei Lan Chen
- , Xiangsheng Huang
- & Mark S. Sundrud
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Article |
Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH
Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps .
- Michael Dudek
- , Dominik Pfister
- & Percy A. Knolle
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Article |
Notch signalling drives synovial fibroblast identity and arthritis pathology
NOTCH3 signalling is shown to be the underlying driver of the differentiation and expansion of a subset of synovial fibroblasts implicated in the pathogenesis of rheumatoid arthritis.
- Kevin Wei
- , Ilya Korsunsky
- & Michael B. Brenner
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Article |
Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation
Analyses of mouse models of inflammation suggest some chronic inflammatory conditions may result from Z-DNA-binding protein 1 sensing endogenous Z-form nucleic acids—such as those of endogenous retroelements—through its Zα domains.
- Huipeng Jiao
- , Laurens Wachsmuth
- & Manolis Pasparakis
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Article |
Gut stem cell necroptosis by genome instability triggers bowel inflammation
In mouse models of bowel inflammation, depletion of the SETDB1 histone methyltransferase leads to genome instability, which releases repression of endogenous retroviruses that triggers ZBP1-dependent necroptosis and inflammation in gut.
- Ruicong Wang
- , Hongda Li
- & Wei Mo
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Letter |
Distinct fibroblast subsets drive inflammation and damage in arthritis
Distinct subsets of fibroblasts, which differ in their expression of thymus cell antigen 1 (THY1), are responsible for inflammation and tissue damage in mouse models of arthritis.
- Adam P. Croft
- , Joana Campos
- & Christopher D. Buckley
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Letter |
Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death
Histone H4 is released from neutrophil extracellular traps and induces membrane lysis in vascular smooth muscle cells, leading to the destabilization of atherosclerotic plaques.
- Carlos Silvestre-Roig
- , Quinte Braster
- & Oliver Soehnlein
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Letter |
Parkin and PINK1 mitigate STING-induced inflammation
Acute and chronic mitochondrial stress in mice require PINK1 and parkin to restrain STING-mediated innate immunity.
- Danielle A. Sliter
- , Jennifer Martinez
- & Richard J. Youle
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Letter |
Allergic inflammatory memory in human respiratory epithelial progenitor cells
Single-cell RNA sequencing is used to characterize cell types in nasal tissues from human patients with chronic rhinosinusitis, revealing a role for tissue stem cells in allergic inflammatory memory.
- Jose Ordovas-Montanes
- , Daniel F. Dwyer
- & Alex K. Shalek
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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 |
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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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 |
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 |
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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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 |
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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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
Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids