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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 |
Recognition and maturation of IL-18 by caspase-4 noncanonical inflammasome
Activated human caspase-4 directly and efficiently processes IL-18 in vitro and during bacterial infections, cleaving the same tetrapeptide site in pro-IL-18 as caspase-1.
- Xuyan Shi
- , Qichao Sun
- & Feng Shao
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Article |
IL-1β+ macrophages fuel pathogenic inflammation in pancreatic cancer
Single-cell and spatial gene expression analyses of pancreatic ductal adenocarcinoma uncover a population of interleukin-1β-expressing macrophages that drive inflammatory reprogramming of neighboring tumour cells leading to disease progression and poor prognosis for patients.
- Nicoletta Caronni
- , Federica La Terza
- & Renato Ostuni
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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
| Open Access
cGAS–STING drives ageing-related inflammation and neurodegeneration
The cGAS–STING signalling pathway is a critical driver of chronic inflammation and functional decline during ageing, and could be targeted to halt neurodegenerative processes during old age.
- Muhammet F. Gulen
- , Natasha Samson
- & Andrea Ablasser
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Article
| Open Access
Structural basis of NINJ1-mediated plasma membrane rupture in cell death
Structural, biochemical and mutagenesis studies indicate that, in dying cells, the membrane protein NINJ1 assembles into filaments, disrupting the cell membrane.
- Morris Degen
- , José Carlos Santos
- & Sebastian Hiller
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Article
| Open Access
A druggable copper-signalling pathway that drives inflammation
Cellular uptake of copper(ii) by CD44 has a key role in regulating cellular plasticity via copper(ii)-dependent downstream signalling events.
- Stéphanie Solier
- , Sebastian Müller
- & Raphaël Rodriguez
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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 |
Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19
Immune responses to influenza vaccination are affected by previous mild COVID-19 in a sex-dimorphic manner.
- Rachel Sparks
- , William W. Lau
- & John S. Tsang
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Article |
Cryo-EM structures of the active NLRP3 inflammasome disc
We report cryogenic electron microscopy structures of disc-shaped active NLRP3 oligomers in complex with NEK7 and ASC, and propose that the role of NEK7 is to transform NLRP3 into the active NLRP3 inflammasome disc.
- Le Xiao
- , Venkat Giri Magupalli
- & Hao Wu
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Article |
ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut
ILC3s expressing MHC class II control the fate of inflammatory versus tolerogenic T cells that respond to the microbiota by selecting for antigen-specific RORγt+ Treg cells and against TH17 cells, establishing intestinal homoeostasis.
- Mengze Lyu
- , Hiroaki Suzuki
- & Gregory F. Sonnenberg
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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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Review Article |
Inflammatory memory and tissue adaptation in sickness and in health
A Review on inflammatory memory in non-immune cells of different epithelia and neurons, and the potential mechanisms controlling these epigenetic memories and their implications in human health and disease.
- Shruti Naik
- & Elaine Fuchs
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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 |
ZBTB46 defines and regulates ILC3s that protect the intestine
A subset of group 3 innate lymphoid cells (ILC3s) expresses the transcription factor ZBTB46—which was previously thought to be restricted to conventional dendritic cells—and these ILC3s have a role in regulating intestinal health.
- Wenqing Zhou
- , Lei Zhou
- & Gregory F. Sonnenberg
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Article
| Open Access
Extricating human tumour immune alterations from tissue inflammation
Complementary single-cell approaches show that a population of regulatory T cells co-expressing ICOS and IL-1 receptor type 1 is highly enriched in tumours but not in site-matched inflamed non-malignant tissue.
- Florian Mair
- , Jami R. Erickson
- & Martin Prlic
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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 |
Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3
Cryo-electron microscopy structures of human NLRP3 in its resting state and bound to the inhibitor CRID3 provide insight into the binding mechanism of CRID3 and its mode of antagonism.
- Inga V. Hochheiser
- , Michael Pilsl
- & Matthias Geyer
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Article |
Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions
Specialized somatosensory neurons that express Gαi-interacting protein (GINIP) promote tissue repair in a model of UV-induced skin damage by secreting the neuropeptide TAFA4, which regulates skin-resident macrophages to release IL-10 and limit fibrosis.
- Guillaume Hoeffel
- , Guilhaume Debroas
- & Sophie Ugolini
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Review Article |
The changing landscape of atherosclerosis
This Review discusses recent research that has transformed our understanding of the biology of atherosclerosis, and examines its implications for the treatment of atherosclerotic cardiovascular disease.
- Peter Libby
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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 |
DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation
Structures of NLRP1–DPP9 alone and with a small-molecule inhibitor of DPP9 reveal the mechanisms through which NLRP1 is regulated, providing insights into the role of this complex in inflammasome regulation.
- L. Robert Hollingsworth
- , Humayun Sharif
- & Hao Wu
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Article |
The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis
Accelerated atherosclerosis in a mouse model of clonal haematopoiesis is prevented by genetic interruption of AIM2 inflammasome activation or by inhibition of interleukin-1β.
- Trevor P. Fidler
- , Chenyi Xue
- & Alan R. Tall
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Article |
MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche
A subset of intestinal stromal cells that is regulated by the kinase MAP3K2 protects intestinal stem cells against injury by producing the WNT agonist R-spondin 1.
- Ningbo Wu
- , Hongxiang Sun
- & Bing Su
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Article |
NINJ1 mediates plasma membrane rupture during lytic cell death
The small transmembrane protein NINJ1 promotes plasma membrane rupture in lytic cell death associated with pyroptosis, necrosis and apoptosis.
- Nobuhiko Kayagaki
- , Opher S. Kornfeld
- & Vishva M. Dixit
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Article |
Galactosaminogalactan activates the inflammasome to provide host protection
Galactosaminogalactan of Aspergillus fumigatus acts as a pathogen-associated molecular pattern that activates the NLRP3 inflammasome, which is crucial for anti-fungal host defence.
- Benoit Briard
- , Thierry Fontaine
- & Thirumala-Devi Kanneganti
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Article |
Exuberant fibroblast activity compromises lung function via ADAMTS4
Viral infection of the respiratory system induces exuberant fibroblast activity, resulting in extensive remodelling of the extracellular matrix and cytokine release, which promote immune cell infiltration of the affected area at the expense of respiratory function.
- David F. Boyd
- , E. Kaitlynn Allen
- & Paul G. Thomas
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Article |
A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis
The dynamic and reversible S-palmitoylation of the transcription factor STAT3 enhances its activation and promotes the differentiation of TH17 cells.
- Mingming Zhang
- , Lixing Zhou
- & Hening Lin
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Article |
Sex differences in immune responses that underlie COVID-19 disease outcomes
Male patients with COVID-19 have higher plasma levels of innate immune cytokines and chemokines such as IL-8, IL-18 and CCL5 and more non-classical monocytes than female patients, whereas female patients mount robust T cell activation maintained even in older age.
- Takehiro Takahashi
- , Mallory K. Ellingson
- & Akiko Iwasaki
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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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Article |
Gasdermin E suppresses tumour growth by activating anti-tumour immunity
The gasdermin E protein is shown to act as a tumour suppressor: it is cleaved by caspase 3 and granzyme B and leads to pyroptosis of cancer cells, provoking an immune response to the tumour.
- Zhibin Zhang
- , Ying Zhang
- & Judy Lieberman
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Review Article |
Pathway paradigms revealed from the genetics of inflammatory bowel disease
This Review examines inflammatory bowel disease in the context of human genetics studies that help to identify pathways that regulate homeostasis of the mucosal immune system and discusses future prospects for disease-subtype classification and therapeutic intervention.
- Daniel B. Graham
- & Ramnik J. Xavier
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Article |
A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1
A dominantly inherited human autoinflammatory disease caused by mutations in RIPK1 is identified, and RIPK1 mutations that prevent caspase-8 cleavage sensitize cells to apoptosis, necroptosis and inflammation.
- Panfeng Tao
- , Jinqiao Sun
- & Qing Zhou
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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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Article |
Colonic epithelial cell diversity in health and inflammatory bowel disease
Profiling of single epithelial cells in healthy and inflamed colons identifies specialized cellular subpopulations, including a type of goblet cell that secretes the antibacterial protein WFDC2, which preserves the integrity of the epithelial barrier layer.
- Kaushal Parikh
- , Agne Antanaviciute
- & Alison Simmons
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Letter |
Sleep modulates haematopoiesis and protects against atherosclerosis
The fragmentation of sleep in Apoe−/− mice induces monocytosis and accelerated atherosclerosis due to a reduction in hypocretin that otherwise restricts bone marrow CSF1 availability.
- Cameron S. McAlpine
- , Máté G. Kiss
- & Filip K. Swirski
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Article |
PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation
Recruitment of NLRP3 to the dispersed trans-Golgi network via binding to PtdIns4P is required for activation of the NLRP3 inflammasome by diverse stimuli.
- Jueqi Chen
- & Zhijian J. Chen
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Letter |
Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release
Distinct transcriptional programs are activated during different stages of apoptotic cell engulfment, including a unique program of genes coding for solute carrier proteins and enzymes in the glycolytic pathway.
- Sho Morioka
- , Justin S. A. Perry
- & Kodi S. Ravichandran
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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 |
New mitochondrial DNA synthesis enables NLRP3 inflammasome activation
New mitochondrial DNA synthesis links the priming and activation of the NLRP3 inflammasome.
- Zhenyu Zhong
- , Shuang Liang
- & Michael Karin
Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids