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Article
| Open AccessAutoreactive T cells target peripheral nerves in Guillain–Barré syndrome
Autoreactive T cells that target myelin antigens in the peripheral nerves are present in patients with the demyelinating form of Guillain–Barré syndrome, and these T cells are likely to contribute to disease pathophysiology.
- L. Súkeníková
- , A. Mallone
- & D. Latorre
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Article
| Open AccessElevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations
Analysis of a large ancient genome dataset shows that genetic risk for multiple sclerosis rose in steppe pastoralists, providing insight into how genetic ancestry from the Neolithic and Bronze Age has shaped modern immune responses.
- William Barrie
- , Yaoling Yang
- & Eske Willerslev
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Article |
RNA editing underlies genetic risk of common inflammatory diseases
cis-RNA editing quantitative trait loci, which are associated with immunogenic double-stranded RNAs, underlie genome-wide association study variants in common autoimmune and inflammatory diseases.
- Qin Li
- , Michael J. Gloudemans
- & Jin Billy Li
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Article |
ADAR1 prevents autoinflammation by suppressing spontaneous ZBP1 activation
In addition to its role in suppressing MDA5 and PKR activation, ADAR1 is a negative regulator of ZPB1-mediated apoptosis and necroptosis, providing insights into the pathology of Aicardi–Goutières syndrome.
- Richard de Reuver
- , Simon Verdonck
- & Jonathan Maelfait
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Article
| Open AccessTwin study reveals non-heritable immune perturbations in multiple sclerosis
In monozygotic twins discordant for multiple sclerosis, the influence of genetic predisposition and environmental factors is determined using matched-pair analyses.
- Florian Ingelfinger
- , Lisa Ann Gerdes
- & Burkhard Becher
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Article |
An autoimmune stem-like CD8 T cell population drives type 1 diabetes
A population of β-cell-specific autoimmune stem-like CD8 T cells initiates and sustains β-cell destruction and disease in a mouse model of type 1 diabetes.
- Sofia V. Gearty
- , Friederike Dündar
- & Andrea Schietinger
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Article |
Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia
Alanine-scanning mutagenesis is used to identify the PF4 epitope that is recognized by anti-PF4 antibodies in patients with vaccine-induced immune thrombotic thrombocytopaenia, revealing that the epitope corresponds to the heparin-binding site on PF4.
- Angela Huynh
- , John G. Kelton
- & Ishac Nazy
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Article |
Genome-wide enhancer maps link risk variants to disease genes
Mapping enhancer regulation across human cell types and tissues illuminates genome function and provides a resource to connect risk variants for common diseases to their molecular and cellular functions.
- Joseph Nasser
- , Drew T. Bergman
- & Jesse M. Engreitz
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Review Article |
Fibrosis: from mechanisms to medicines
This review discusses how single-cell profiling and other technological advances are increasing our understanding of the mechanisms of fibrosis, thereby accelerating the discovery, development and testing of new treatments.
- Neil C. Henderson
- , Florian Rieder
- & Thomas A. Wynn
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Article |
FLT3 stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease
A predicted loss-of-function germline mutation in FLT3 causes a reduction in full-length FLT3, with a compensatory increase in the levels of FLT3 ligand, leading to increased risk of autoimmune thyroid disease.
- Saedis Saevarsdottir
- , Thorunn A. Olafsdottir
- & Kari Stefansson
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Article |
Complement genes contribute sex-biased vulnerability in diverse disorders
Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.
- Nolan Kamitaki
- , Aswin Sekar
- & Steven A. McCarroll
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Article |
IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease
An HLA- and gluten-dependent mouse model of coeliac disease with villous atrophy provides evidence for the cooperative role of IL-15 and gluten-specific CD4+ T cells in licensing the full activation of cytotoxic T cells that are necessary for inducing epithelial damage.
- Valérie Abadie
- , Sangman M. Kim
- & Bana Jabri
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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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Article |
Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease
Heterozygous mutateons in the caspase-8 cleavage site of RIPK1 cause a range of autoinflammatory symptoms in humans, and caspase-8 cleavage of RIPK1 in a mouse model limits TNF-induced cell death and inflammation.
- Najoua Lalaoui
- , Steven E. Boyden
- & John Silke
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Letter |
Locally renewing resident synovial macrophages provide a protective barrier for the joint
Analysis of macrophage subsets within joints reveals a population of CX3CR1+ tissue-resident macrophages that form a tight-junction-mediated barrier at the synovial lining, protecting the joint from the invasion of inflammatory cells.
- Stephan Culemann
- , Anika Grüneboom
- & Gerhard Krönke
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Perspective
| Open AccessThe Integrative Human Microbiome Project
Over ten years, the Human Microbiome Project has provided resources for studying the microbiome and its relationship to disease; this Perspective summarizes the key achievements and findings of the project and its relationship to the broader field.
- Lita M. Proctor
- , Heather H. Creasy
- & Curtis Huttenhower
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Letter
| Open AccessThe human gut microbiome in early-onset type 1 diabetes from the TEDDY study
An analysis of more than 10,000 metagenomes from the TEDDY study provides a detailed functional profile of the gut microbiome in relation to islet autoimmunity, and supports the protective effects of short-chain fatty acids in early-onset type 1 diabetes.
- Tommi Vatanen
- , Eric A. Franzosa
- & Ramnik J. Xavier
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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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Letter |
Pancreatic islets communicate with lymphoid tissues via exocytosis of insulin peptides
A sensitive T cell tracking assay reveals immunogenic activity of specific catabolized peptide fragments of insulin and their effects on T cell activity in lymph nodes, highlighting communication between pancreatic islets and lymphoid tissue.
- Xiaoxiao Wan
- , Bernd H. Zinselmeyer
- & Emil R. Unanue
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Letter |
Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host
Microbial signals are crucial to the development of pre-leukaemic myeloproliferation, which can be induced by disrupting the intestinal barrier or by introducing systemic bacterial stimuli in Tet2-deficient mice.
- Marlies Meisel
- , Reinhard Hinterleitner
- & Bana Jabri
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Article |
Salt-responsive gut commensal modulates TH17 axis and disease
High salt intake changed the gut microbiome and increased TH17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of TH17 cells and increased blood pressure in humans.
- Nicola Wilck
- , Mariana G. Matus
- & Dominik N. Müller
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Article |
Fine-mapping inflammatory bowel disease loci to single-variant resolution
Results of fine-mapping 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals and several new fine-mapping methods.
- Hailiang Huang
- , Ming Fang
- & Jeffrey C. Barrett
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Letter |
Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis
The authors identify in patients with rheumatoid arthritis a pathogenic subset of CD4+ T cells that augments B cell responses within inflamed tissues.
- Deepak A. Rao
- , Michael F. Gurish
- & Michael B. Brenner
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Outlook |
Q&A: Joel Weinstock
Helminths are worms that can live in the human intestine. Joel Weinstock, a gastroenterologist at Tufts Medical Center in Boston, Massachusetts, studies how they affect inflammation and the body's immune response. He spoke to Nature about how helminths might lead to treatments for inflammatory bowel disease (IBD).
- Neil Savage
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Outlook |
Genetics: Clues in the code
Gene exploration is providing unexpected insights into inflammatory bowel disease, and getting scientists closer to finding treatments that target the biological mechanisms.
- Sarah DeWeerdt
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Outlook |
Cell-based therapy: Cells on trial
Four regenerative and immune-system therapies taking on the toughest cases of inflammatory bowel disease.
- Eric Bender
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Outlook |
Microbiota: Reseeding the gut
Transplants of faecal matter have done wonders for the treatment of certain gastrointestinal infections. Will they ever work for inflammatory bowel disease?
- Liam Drew
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Article |
Expanding antigen-specific regulatory networks to treat autoimmunity
Nanoparticles coated with autoantigenic peptides bound to MHC class II molecules suppress established autoimmune disease by inducing antigen-specific TR1-like regulatory T cells in mouse and humanized mouse models.
- Xavier Clemente-Casares
- , Jesus Blanco
- & Pere Santamaria
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Letter |
Clinical improvement in psoriasis with specific targeting of interleukin-23
A proof-of-concept phase I clinical trial demonstrates that targeting interleukin (IL)-23 with an antibody that binds to the p19 subunit leads to clinical improvement of disease in patients with moderate to severe psoriasis.
- Tamara Kopp
- , Elisabeth Riedl
- & Sauzanne Khalilieh
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Letter |
Super-enhancers delineate disease-associated regulatory nodes in T cells
A study of the super-enhancer landscape in three mouse T-helper lymphocyte subsets identifies nodes that have key roles in cell identity, with the locus encoding Bach2, a key negative regulator of effector differentiation, emerging as the most prominent T-cell super-enhancer.
- Golnaz Vahedi
- , Yuka Kanno
- & John J. O’Shea
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Letter |
Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions
Cationic substances, including some drugs, can activate mast cells in an IgE-independent manner, leading to histamine release, inflammation and airway contraction; here, the G-protein-coupled receptor MrgprB2, the orthologue of human MRGPRX2, is shown to be the sole mast cell receptor for these substances in mice.
- Benjamin D. McNeil
- , Priyanka Pundir
- & Xinzhong Dong
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Letter |
IgG1 protects against renal disease in a mouse model of cryoglobulinaemia
Here, the predominant murine immunoglobulin G subclass, IgG1, which is a poor activator of effector mechanisms, is shown to have a regulatory function, protecting against the development of IgG3 immune-complex-driven renal disease by competing with IgG3 for antigen and increasing immune complex solubility.
- Richard T. Strait
- , Monica T. Posgai
- & Fred D. Finkelman
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Letter |
Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation
ISG15 deficiency in humans leads to a failure to maintain adequate levels of USP18, triggering an increase in type I interferon production and signalling, and promoting auto-inflammatory disease.
- Xianqin Zhang
- , Dusan Bogunovic
- & Sandra Pellegrini
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Letter |
CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation
Loss-of-function mutations in the human CTP synthase 1 gene cause an immunodeficiency disease with impaired T cell proliferation after antigen stimulation, revealing a potential new target for immunosuppressive drugs.
- Emmanuel Martin
- , Noé Palmic
- & Sylvain Latour
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Letter |
Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma
Failure of integrin-mediated cell-matrix attachment is sufficient to initiate dermal fibrosis and autoimmunity in mouse models of scleroderma; integrin-modulating therapies prevent the recruitment and activation of plasmacytoid dendritic cells that appear central to immunological dysregulation and maintenance of the pro-fibrotic synthetic programme.
- Elizabeth E. Gerber
- , Elena M. Gallo
- & Harry C. Dietz
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Letter |
BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis
Diverse autoimmune and allergic diseases are associated with polymorphisms in a locus encoding the transcription factor BACH2; here, BACH2 is shown to be a broad regulator of immune activation that stabilizes the differentiation of Treg cells by repressing commitment of CD4+ T cells to alternate cell fates.
- Rahul Roychoudhuri
- , Kiyoshi Hirahara
- & Nicholas P. Restifo
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Letter |
Negligible impact of rare autoimmune-locus coding-region variants on missing heritability
A search for variants in coding exons of 25 genome-wide association study risk genes in a large cohort of autoimmune patients finds that rare coding-region variants at known loci have a negligible role in common autoimmune disease susceptibility, arguing against the previously proposed rare-variant synthetic genome-wide association hypothesis.
- Karen A. Hunt
- , Vanisha Mistry
- & David A. van Heel
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Review Article |
Macrophage biology in development, homeostasis and disease
A discussion of progress in macrophage biology, examining their classification, diverse lineages, identities and regulation, their roles in regulating normal physiology and development, and their identification as therapeutic targets in human diseases.
- Thomas A. Wynn
- , Ajay Chawla
- & Jeffrey W. Pollard
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Outlook |
Psoriasis uncovered
Science is finally getting to grips with this enigmatic autoimmune disease.
- James Mitchell Crow
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Outlook |
Therapeutics: Silencing psoriasis
The latest drugs hold fantastic promise for people with severe psoriasis. But where are the treatment options for the far larger number with less serious cases?
- James Mitchell Crow
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Outlook |
Psychodermatology: An emotional response
As the link between stress and psoriasis flare-ups becomes clearer, it seems the most vulnerable patients require a new type of treatment.
- Sarah DeWeerdt
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Outlook |
Q&A: Under their skin
Psoriasis can have a profound impact on patients' emotional and social lives. Christopher Griffiths, a dermatologist at the University of Manchester in the United Kingdom, discusses the disease's psychological fallout and its links with stress.
- Christopher Griffiths
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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 |
Genetics: Deep exploration
Recent discoveries are redefining the role of the immune system in psoriasis, and may help to unravel the mystery of the disease's origins.
- Ken Garber
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Outlook |
Microbiome: The surface brigade
Our skin is home to thousands of species of bacteria — and when these microscopic societies are disrupted, skin infections can arise.
- Bijal Trivedi
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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 |
Interleukin receptor activates a MYD88–ARNO–ARF6 cascade to disrupt vascular stability
Interleukin-1β-induced disruption to endothelial stability and vascular permeability in a human in vitro model is shown to be independent of downstream nuclear factor-κB activation, relying instead on a MYD88–ARNO–ARF6 signalling cascade; inhibiting proteins involved in this pathway is shown to improve outcomes in animal models of inflammatory disease.
- Weiquan Zhu
- , Nyall R. London
- & Dean Y. Li