Autoimmunity articles within Nature Communications

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  • Article
    | Open Access

    CD39 is an ectonucleotidase associated with immunoregulatory function. Here authors show regulation of CD39 expression by an endogenous antisense RNA moiety transcribed from the 3‘ end of CD39/ENTPD1 which when itself is silenced results in amelioration of pathology in an animal model of colitis.

    • Rasika P. Harshe
    • , Anyan Xie
    •  & Maria Serena Longhi

  • Article
    | Open Access

    Systemic sclerosis (SSc) is a disease with manifestation in the skin and immune etiology, but the pathogenic immune cell types remain unidentified. Here the authors use ATAC-seq to profile chromatin landscapes of skin samples from patients with SSc to implicate skin dendritic cells for having the strongest disease-associated epigenetic changes.

    • Qian Liu
    • , Lisa C. Zaba
    •  & Howard Y. Chang

  • Article
    | Open Access

    How mutations in the microbial receptor NOD2 induce Blau syndrome in humans and related uveitis is unclear. Here the authors show, using Nod2-deficient mice and experimental uveitis, that Nod2 negatively regulates T cell activation and transcription of autoimmunity-related genes to suppress Th17 responses and uveitis.

    • Ruth J. Napier
    • , Ellen J. Lee
    •  & Holly L. Rosenzweig

  • Article
    | Open Access

    SOCS1 is a potent suppressor of JAK-STAT signalling responses to IFNγ and γ-chain cytokines and thereby limits inflammation. Here the authors identify and characterize heterozygous SOCS1 mutations in 10 patients from 5 unrelated families with autoimmune diseases.

    • Jérôme Hadjadj
    • , Carla Noemi Castro
    •  & Frédéric Rieux-Laucat

  • Article
    | Open Access

    Psoriatic arthritis (PsA) commonly affects patients with skin psoriasis, but its pathogenesis is still unclear. Here the authors use two types of single-cells data, mass cytometry and RNA sequencing, to describe the expansion and diversity of synovial, but not peripheral blood, CD8 T cells from PsA patients to provide a molecular immune landscape for PsA.

    • Frank Penkava
    • , Martin Del Castillo Velasco-Herrera
    •  & M. Hussein Al-Mossawi

  • Article
    | Open Access

    How extracellular calcium can trigger Nlrp3 inflammasome activation has been somewhat controversial and unclear. Here the authors show calciprotein particles are taken up by myeloid cells via calcium-sensing receptor-dependent macropinocytosis in response to high levels of extracellular Ca2+ and this pathway might be critical to inflammatory conditions.

    • Elisabeth Jäger
    • , Supriya Murthy
    •  & Ulf Wagner

  • Article
    | Open Access

    Type I IFN has apposing effects in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Here the authors perform molecular profiling of NMOSD patients and mouse mechanistic experiments of neuro-inflammation to show that IFN-I stimulates pathogenic Th17 via IL-6 production by B cells.

    • Agnieshka M. Agasing
    • , Qi Wu
    •  & Robert C. Axtell

  • Article
    | Open Access

    Splenic marginal zone macrophages can establish immune tolerance and limit the development of systemic lupus erythematosus (SLE). Here the authors show that these cells do this by clearing apoptotic cells, and defects in these cells result in the generation of self-reactive double negative T cells that are known to contribute to SLE pathogenesis.

    • Hao Li
    • , Iannis E. Adamopoulos
    •  & George C. Tsokos

  • Article
    | Open Access

    Type 1 diabetes is associated with autoimmune destruction of pancreatic beta-cells. Here the authors compose a large-scale electron microscopy image data base of pancreatic organ donor tissue to enable data mining and further understanding of the disease.

    • Pascal de Boer
    • , Nicole M. Pirozzi
    •  & Ben N. G. Giepmans

  • Article
    | Open Access

    Immune tolerance is mediated by the deletion of autoreactive T cells via medullary thymic epithelial cells (mTEC) and dendritic cells (DC), and by the induction of regulatory T cells (Treg). Here the authors show that mTEC receiving toll-like receptor signaling control the recruitment of CD14+Sirpα+ DC population that is capable of inducing Treg for establishing tolerance.

    • Matouš Vobořil
    • , Tomáš Brabec
    •  & Dominik Filipp

  • Article
    | Open Access

    Intestinal dysbiosis is associated with an ever-growing list of autoimmune diseases. Here the authors show that both mice and humans with autoimmune arthritis can have dysbiosis and barrier leakiness prior to major signs of inflammatory arthritis, and treatment of mice with a zonulin antagonist can limit collagen-induced arthritis.

    • Narges Tajik
    • , Michael Frech
    •  & Mario M. Zaiss

  • Article
    | Open Access

    Moderate consumption of alcohol is associated with protection from some autoimmune diseases. Here the authors show that ethanol and its metabolite acetate can protect mice from collagen-induced arthritis and provide evidence that the mechanism of this effect might be via inhibition of the effector function of T follicular helper cells.

    • Vugar Azizov
    • , Katharina Dietel
    •  & Mario M. Zaiss

  • Article
    | Open Access

    α-Synuclein-specific T cell reactivity is preferentially associated with Parkinson’s disease (PD) patients, but the temporal relation with diagnosis was previously unknown. This study reveals that α-syn-reactive T cells are highest before and shortly after diagnosis of motor PD, and then decrease.

    • Cecilia S. Lindestam Arlehamn
    • , Rekha Dhanwani
    •  & Alessandro Sette

  • Article
    | Open Access

    Circadian rhythms can alter inflammatory state and activity of inflammatory diseases such as rheumatoid arthritis. Here the authors show that extrinsic signals confer a circadian rhythm to regulatory T cell activity, which in turn drives rhythmic inflammation in collagen-induced arthritis.

    • L. E. Hand
    • , K. J. Gray
    •  & J. E. Gibbs

  • Article
    | Open Access

    Membranous nephropathy (MN) is a rare autoimmune disease of podocyte-directed antibodies, such as anti-phospholipase A2 receptor. Here, the authors report a genome-wide association study for MN and identify two previously unreported loci encompassing the NFKB1 and IRF4 genes and additional ancestry-specific effects.

    • Jingyuan Xie
    • , Lili Liu
    •  & Krzysztof Kiryluk

  • Article
    | Open Access

    Here the authors provide a single-cell characterization of cerebrospinal fluid and blood of newly diagnosed multiple sclerosis (MS) patients, revealing altered composition of lymphocyte and monocyte subsets, validated by other methods including the interrogation of the TFH subset in mouse models of MS.

    • David Schafflick
    • , Chenling A. Xu
    •  & Gerd Meyer zu Horste

  • Article
    | Open Access

    . TGFβ is critical for limiting autoreactive responses of peripheral T cells. Here, the authors show that TGFβ signaling in thymocytes mediates elimination of self-reactive T cells and promotes the expression of self-antigens by medullary thymic epithelial cells.

    • Mark J. McCarron
    • , Magali Irla
    •  & Julien C. Marie

  • Article
    | Open Access

    Susac syndrome is an inflammatory pathology of the brain endothelium. Here the authors show that the pathology is driven by CD8 T cells attacking the endothelium, and that blocking T cell-endothelial adhesion ameliorates the disease in a mouse model, and associates with improved clinical score in 4 patients.

    • Catharina C. Gross
    • , Céline Meyer
    •  & Roland Liblau

  • Article
    | Open Access

    Dimethyl fumarate (DMF) is a therapy for multiple sclerosis (MS) with undetermined mechanism of action. Here the authors find that clinical response to DMF associates with decrease in IL-17-producing CD8+ T cells (Tc17), delineate molecular pathways involved, and show that DMF suppresses Tc17 pathogenicity in a mouse model of MS.

    • Christina Lückel
    • , Felix Picard
    •  & Magdalena Huber

  • Article
    | Open Access

    Innate immune cells can be trained by some stimuli or pathogen exposures to be metabolically and epigenetically altered such that they have different responses to subsequent exposures. Here the authors show that low-dose LPS trained macrophages and BCG-trained macrophages have opposing effects on fibrosis and inflammation in the context of systemic sclerosis.

    • Mohamed Jeljeli
    • , Luiza Gama Coelho Riccio
    •  & Frédéric Batteux

  • Article
    | Open Access

    Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder characterised by asthma, eosinophilia and vasculitis. Here, the authors describe a genome-wide association study of EGPA that reveals clinical and genetic differences between subgroups stratified by autoantibody status (ANCA).

    • Paul A Lyons
    • , James E Peters
    •  & Kenneth G. C. Smith

  • Article
    | Open Access

    MHC-I-induced signalling of various natural killer (NK) inhibitory receptors is critical for regulation NK cell education, but clear genetic evidence is still lacking. Here the authors generate multiple lines of mice differentially deficient in Ly49 family and/or NKG2A NK receptors, and find that self-MHCI specific Ly49 members and NKG2A synergize to regulate NK education.

    • Xiaoqian Zhang
    • , Jin Feng
    •  & Zhongjun Dong

  • Article
    | Open Access

    Recombinant MHC class II molecules are instrumental in antigen-specific T-cell identification assays and showed efficacy as experimental medicines. Here, the authors engineer MHC class II molecules with species-specific knob-into-hole heteromerization domains, enabling a translatable purification process with improved stability, yields, and biological potency.

    • Pau Serra
    • , Nahir Garabatos
    •  & Pere Santamaria

  • Article
    | Open Access

    Food intake shapes intestinal microbiome composition, which in turn shapes adaptive immune responses. Here the authors show that dietary tryptophan restriction (DTR) protects mice from subsequent autoimmune neuropathology challenge by altering intestinal microbiota, highlighting the potential of diet-regulated microbiota to prevent immune pathology.

    • Jana K. Sonner
    • , Melanie Keil
    •  & Michael Platten

  • Article
    | Open Access

    How antibody reaches tissues from circulation is critical for understanding antibody-mediated immunity. Here the authors show that IgG extravasation in the skin is mediated by endothelial caveolin transport independently of FcR, and is targetable by imatinib, which reduces IgG-dependent pathology in a mouse model of pemphigus.

    • Sachiko Ono
    • , Gyohei Egawa
    •  & Kenji Kabashima

  • Article
    | Open Access

    B cell response and antibody production are generally facilitated by CD4+ follicular helper (Tfh) cells. Here the authors identify a subset of CXCR5+PD1+CD8+ Tfh cells that is normally suppressed by STAT5 signaling, so that STAT5 deficiency in mice increases the number of these CD8+ Tfh cells and induces concomitant production of autoantibodies.

    • Yuhong Chen
    • , Mei Yu
    •  & Demin Wang

  • Article
    | Open Access

    Complex traits associate with genetic variation and environment and their interaction. Here, the authors study the influence of different diets on trait variability in 1154 outbred mice from an advanced intercross line and find gene-diet interactions associated with spontaneous autoimmunity development in these animals.

    • Artem Vorobyev
    • , Yask Gupta
    •  & Ralf J. Ludwig

  • Article
    | Open Access

    Statistical fine-mapping to pinpoint likely causal variants in a genomic region is complicated by linkage disequilibrium (LD). Here, Asimit et al. compare stepwise and stochastic approaches to fine-mapping and propose a Bayesian multinomial stochastic search method which they apply to six immune-mediated diseases.

    • Jennifer L. Asimit
    • , Daniel B. Rainbow
    •  & Chris Wallace

  • Article
    | Open Access

    Function-altering variants of immune-related genes cause rare autoimmune syndromes, whereas their contribution to common autoimmune diseases remains uncharacterized. Here the authors show that rare variants of lupus-associated genes are present in the majority of lupus patients and healthy controls, but only the variants found in lupus patients alter gene function.

    • Simon H. Jiang
    • , Vicki Athanasopoulos
    •  & Carola G. Vinuesa

  • Article
    | Open Access

    Tissue signals that prime autoreactive T cells at the onset of autoimmunity remain enigmatic. Here the authors show NK and ILC1 cells are increased in vitiligo patients, and induce melanocyte apoptosis via CXCR3B, which in turn leads to increased priming of T cell responses in cell culture.

    • Meri K. Tulic
    • , Elisa Cavazza
    •  & Thierry Passeron

  • Article
    | Open Access

    Monozygotic (MZ) twins are ideal to study the influence of non-genetic factors on complex phenotypes. Here, Souren et al. perform an EWAS in peripheral blood mononuclear cells from 45 MZ twins discordant for multiple sclerosis and identify disease and treatment-associated epigenetic markers.

    • Nicole Y. Souren
    • , Lisa A. Gerdes
    •  & Jörn Walter

  • Article
    | Open Access

    CXCL4 is an inflammatory chemokine signaling through CXCR3 receptor. Here the authors show a CXCR3-independent function of CXCL4: it forms liquid crystals with DNA, potentiating mammalian and bacterial DNA recognition by TLR9, thereby amplifying interferon-a production in systemic sclerosis.

    • Roberto Lande
    • , Ernest Y. Lee
    •  & Loredana Frasca

  • Article
    | Open Access

    The inhibitory receptor, FcγRIIb, is reported to limit autoimmune B cell response. Here the authors show that FcγRIIb has a dual role in both human and mouse, with reduced FcγRIIb expression or function associated with enhanced pre-immune B cell tolerance, yet defective control of mature autoreactive B cells in the germinal center.

    • Marion Espéli
    • , Rachael Bashford-Rogers
    •  & Kenneth G. C. Smith

  • Article
    | Open Access

    Antiphospholipid syndrome is characterised by increased neutrophil extracellular trap formation (NETosis) and, consequently, increased thrombotic events. Here Ali et al. show that treatment with adenosine receptor agonists suppresses NETosis and venous thrombosis in mouse models of antiphospholipid syndrome.

    • Ramadan A. Ali
    • , Alex A. Gandhi
    •  & Jason S. Knight

  • Article
    | Open Access

    Interleukin-2 (IL-2) signaling is required for regulatory T (Treg) cell differentiation in the thymus, but its function in peripheral Tregs is still unclear. Here the authors show, using inducible deletion of IL-2 receptor subunit CD25, that IL-2 signaling is essential for maintaining peripheral Treg homeostasis, but dispensable for lineage stability.

    • Kevin H. Toomer
    • , Jen Bon Lui
    •  & Thomas R. Malek

  • Article
    | Open Access

    Autoreactive T cells are suspected to destroy hypocretin-producing neurons in narcolepsy. Here the authors detect CD8 T cells recognizing narcolepsy-related proteins in healthy individuals and in patients with narcolepsy, and show that the frequency of self-reactive CD8 T cells differs between patients and controls sharing the same HLA-II risk allele.

    • Natasja Wulff Pedersen
    • , Anja Holm
    •  & Birgitte Rahbek Kornum

  • Article
    | Open Access

    Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are still unclear. Here the authors show that a SCFA, pentanoate, suppresses autoimmune inflammation in mouse models of colitis and multiple sclerosis via epigenetic modulation of immune cell metabolic and functional pathways.

    • Maik Luu
    • , Sabine Pautz
    •  & Alexander Visekruna

  • Article
    | Open Access

    Ubiquitination may control protein stability or function. Here the authors show that an ubiquitination enzyme, Hectd3, ubiquitinates Stat3 and Malt1 to modulate their function but not degradation in T cells, and thereby promoting the differentiation of pathogenic Th17 cells and susceptibility to a mouse model of multiple sclerosis.

    • Jonathan J. Cho
    • , Zhiwei Xu
    •  & Dorina Avram

  • Article
    | Open Access

    A chromatin remodelling factor Satb1 is essential for T cell lineage development in the thymus. Here the authors show that while Satb1 is dispensable for the differentiation of Th17 cells and their response to gut commensals, it plays a critical role in pathogenic Th17 effector function in EAE by directly activating Bhlhe40 and modulating PD-1.

    • Keiko Yasuda
    • , Yohko Kitagawa
    •  & Keiji Hirota

  • Article
    | Open Access

    Natural killer (NK) cells are functionally calibrated against self MHC during a process termed education. Here the authors show that NK cell education is associated with the accumulation of dense-core secretory lysosomes for expedited release of granzyme B and Ca2+ flux upon target recognition and NK cell activation.

    • Jodie P. Goodridge
    • , Benedikt Jacobs
    •  & Karl-Johan Malmberg

  • Article
    | Open Access

    The transcription factor Foxp3 and Stat5 modulate lineage stability and function of regulatory T (Treg) cells to promote immune homeostasis. Here the authors show that O-GlcNAcylation of Foxp3 and Stat5, mediated by O-GlcNAc transferase (OGT), is essential for Treg-mediate immune balance, with Treg-specific deficiency of OGT leading to severe autoimmunity.

    • Bing Liu
    • , Oscar C. Salgado
    •  & Hai-Bin Ruan

  • Article
    | Open Access

    B cells produce antibodies to mediate various immune functions, but are also reported to negatively regulate immune responses. Here, the authors show that a subset of mature B cells expressing low levels of IgD, present in both mice and human, may pursue this regulatory function indirectly by inducing the proliferation of regulatory T cells via GITRL.

    • Avijit Ray
    • , Mohamed I. Khalil
    •  & Bonnie N. Dittel

  • Article
    | Open Access

    Regulatory T (Treg) cells are developed in the thymus, and are essential for suppressing detrimental autoimmunity. Here the authors show, using mice with dampened interleukin 2 (IL-2) signaling, that IL-2 helps position the pioneer factor SATB1 to control genome-wide chromatin accessibility to facilitate Treg cell lineage commitment in the thymus.

    • Laurent Chorro
    • , Masako Suzuki
    •  & Grégoire Lauvau

  • Article
    | Open Access

    It is unclear if multiple sclerosis (MS) genetic susceptibility can be mediated through perturbations of CNS-intrinsic pathways. Authors show that the rs7665090 risk variant is associated with astrocyte responses that enhance lymphocyte recruitment, and with increased lymphocyte infiltration and lesion sizes in MS lesions.

    • Gerald Ponath
    • , Matthew R. Lincoln
    •  & David Pitt

  • Article
    | Open Access

    Regulatory T (Treg) cells need to be differentiated into effector Treg (eTreg), with the transcription factor IRF4 implicated during this process. Here the authors show that an AP-1 family transcription factor, JunB, is expressed in eTreg to promote the IRF4 transcription program, and regulate eTreg homeostasis and function.

    • Shin-ichi Koizumi
    • , Daiki Sasaki
    •  & Hiroki Ishikawa

  • Article
    | Open Access

    Autoantibodies are implicated in autoimmunity, but may also be present in healthy individuals. Here the authors find that the autoantibody specificity signatures against various G protein-coupled receptors are associated with multiple parameters, including disease states, to imply a physiological function in maintaining immune homeostasis.

    • Otavio Cabral-Marques
    • , Alexandre Marques
    •  & Gabriela Riemekasten

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