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BMC Immunology Oct 2023Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic...
Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic variation, immunological dysfunction, and various environmental factors. To improve our understanding of the mechanisms behind digestive autoimmune conditions, including factors causing gastrointestinal manifestations and pathogenesis, BMC Immunology has launched a new Collection "The digestive system and autoimmunity".
Topics: Humans; Autoimmunity; Autoimmune Diseases; Digestive System
PubMed: 37794375
DOI: 10.1186/s12865-023-00561-4 -
Journal of Autoimmunity May 2023Infections are known to trigger flares of autoimmune diseases in humans and serve as an inciting cause of autoimmunity in animals. Evidence suggests a causative role of... (Review)
Review
Infections are known to trigger flares of autoimmune diseases in humans and serve as an inciting cause of autoimmunity in animals. Evidence suggests a causative role of infections in triggering antigen-specific autoimmunity, previous thought mainly through antigen mimicry. However, an infection can induce bystander autoreactive T and B cell polyclonal activation, believed to result in non-pathogenic and pathogenic autoimmune responses. Lastly, epitope spreading in autoimmunity is a mechanism of epitope changes of autoreactive cells induced by infection, promoting the targeting of additional self-epitopes. This review highlights recent research findings, emphasizes infection-mediated autoimmune responses, and discusses the possible mechanisms involved.
Topics: Humans; Animals; Autoimmunity; Autoantibodies; Autoimmune Diseases; Epitopes; Communicable Diseases
PubMed: 36470769
DOI: 10.1016/j.jaut.2022.102962 -
Nature Reviews. Immunology Feb 2023Self-reactive immune responses occur in autoimmune diseases and also in chronic inflammatory and metabolic diseases that are not generally considered as autoimmune...
Self-reactive immune responses occur in autoimmune diseases and also in chronic inflammatory and metabolic diseases that are not generally considered as autoimmune diseases. How do the mechanisms of autoreactivity in the different settings overlap and how are they distinguished? Evidence indicates that while autoimmune diseases rely on both a supportive genetic background and a cooperative environment, chronic inflammatory and metabolic diseases strongly hinge on a conducive milieu for the activation of pathogenic autoreactive cells even in the absence of facilitating polygenic factors.
Topics: Humans; Autoimmunity; Autoantibodies
PubMed: 36418434
DOI: 10.1038/s41577-022-00812-2 -
Annual Review of Immunology 2012Monogenic autoimmune syndromes provide a rare yet powerful glimpse into the fundamental mechanisms of immunologic tolerance. Such syndromes reveal not only the... (Review)
Review
Monogenic autoimmune syndromes provide a rare yet powerful glimpse into the fundamental mechanisms of immunologic tolerance. Such syndromes reveal not only the contribution of an individual breakpoint in tolerance but also patterns in the pathogenesis of autoimmunity. Disturbances in innate immunity, a system built for ubiquitous sensing of danger signals, tend to generate systemic autoimmunity. For example, defects in the clearance of self-antigens and chronic stimulation of type 1 interferons lead to the systemic autoimmunity seen in C1q deficiency, SPENCDI, and AGS. In contrast, disturbances of adaptive immunity, which is built for antigen specificity, tend to produce organ-specific autoimmunity. Thus, the loss of lymphocyte homeostasis, whether through defects in apoptosis, suppression, or negative selection, leads to organ-specific autoimmunity in ALPS, IPEX, and APS1. We discuss the unique mechanisms of disease in these prominent syndromes as well as how they contribute to the spectrum of organ-specific or systemic autoimmunity. The continued study of rare variants in autoimmune disease will inform future investigations and treatments directed at rare and common autoimmune diseases alike.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Humans; Immunologic Deficiency Syndromes; Organ Specificity
PubMed: 22224765
DOI: 10.1146/annurev-immunol-020711-074953 -
Frontiers in Immunology 2021
Topics: Animals; Autoimmunity; Bacteria; Humans; Viruses
PubMed: 34567014
DOI: 10.3389/fimmu.2021.752980 -
Trends in Molecular Medicine Feb 2011The NOD-like receptor (NLR) family members are cytosolic sensors of microbial components and danger signals. A subset of NLRs control inflammasome assembly that results... (Review)
Review
The NOD-like receptor (NLR) family members are cytosolic sensors of microbial components and danger signals. A subset of NLRs control inflammasome assembly that results in caspase-1 activation and, in turn, IL-1β and IL-18 production. Excessive inflammasome activation can cause autoinflammatory disorders, including the hereditary periodic fevers. Autoinflammatory and autoimmune diseases form a disease spectrum of aberrant, immune-mediated inflammation against self, through innate and adaptive immunity. However, the role of inflammasomes in autoimmune disease is less clear than in autoinflammation, despite the numerous effects IL-1β and IL-18 can have on shaping adaptive immunity. We summarize the role of inflammasomes in autoimmune disorders, highlight the need for a better understanding of inflammasomes in these conditions and offer suggestions for future research directions.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Humans; Inflammasomes
PubMed: 21163704
DOI: 10.1016/j.molmed.2010.11.001 -
Autoimmunity Reviews May 2021The glycosylation of the fragment crystallizable (Fc) region of immunoglobulins (Ig) is critical for the modulation of antibody effects on inflammation. Moreover,... (Review)
Review
The glycosylation of the fragment crystallizable (Fc) region of immunoglobulins (Ig) is critical for the modulation of antibody effects on inflammation. Moreover, antibody glycosylation may induce pathologic modifications and ultimately contribute to the development of autoimmune diseases. Thanks to progress in the analysis of glycosylation, more data are available on IgG and its subclass structures in the context of autoimmune diseases. In this review, we focused on the impact of Ig glycosylation in autoimmunity, describing how it modulates the immune response and how glycome profiles can be used as biomarkers of disease activity. The analysis of antibody glycosylation demonstrated specific features in human autoimmune and chronic inflammatory conditions, including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and autoimmune liver diseases, among others. Within the same disease, different patterns are associated with disease severity and treatment options. Future research may increase the information available on the distinct glycome profiles and expand their potential role as biomarkers and as targets for treatment, ultimately favoring an individualized approach.
Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Autoimmunity; Glycosylation; Humans; Lupus Erythematosus, Systemic
PubMed: 33727152
DOI: 10.1016/j.autrev.2021.102804 -
Cold Spring Harbor Perspectives in... Mar 2013The commensal microbiota affects many aspects of mammalian health including control of the immune system to such a extent that a "commensalocentric" view of the... (Review)
Review
The commensal microbiota affects many aspects of mammalian health including control of the immune system to such a extent that a "commensalocentric" view of the maintenance of overall health could be suggested. Autoimmunity is a case of mistaken identity: The immune system reacts to self-tissues and cells as if they were pathogens. Autoimmune reactions can be both advanced or blocked by the commensal microbiota, which can affect innate and adaptive arms of immune responses as well as the mechanisms of "innate-adaptive connection." Whether specific microbial lineages affect immunity and autoimmunity (the "specific lineage hypothesis") or multiple lineages can tip the homeostatic balance that regulates host/microbiota homeostasis toward reduced or enhanced host reactivity (the "balanced signal hypothesis") is yet unknown. The complexity of host/microbiota interactions needs to be fully appreciated in order to find the means for prophylaxis and treatment of autoimmune disorders.
Topics: Autoimmunity; Environment; Gastrointestinal Tract; Homeostasis; Host-Pathogen Interactions; Humans; Metagenome; Models, Immunological; Signal Transduction; Species Specificity
PubMed: 23457255
DOI: 10.1101/cshperspect.a007294 -
PLoS Medicine Aug 2006The formal recognition and genetic understanding of the autoinflammatory diseases has defined mechanisms of self-directed inflammation that are independent of adaptive...
The formal recognition and genetic understanding of the autoinflammatory diseases has defined mechanisms of self-directed inflammation that are independent of adaptive immunity.
Topics: Arthritis, Psoriatic; Autoimmunity; Humans; Immune System Diseases; Inflammation
PubMed: 16942393
DOI: 10.1371/journal.pmed.0030297 -
Nature Communications Sep 2017Cyclic GMP-AMP synthase is essential for innate immunity against infection and cellular damage, serving as a sensor of DNA from pathogens or mislocalized self-DNA. Upon...
Cyclic GMP-AMP synthase is essential for innate immunity against infection and cellular damage, serving as a sensor of DNA from pathogens or mislocalized self-DNA. Upon binding double-stranded DNA, cyclic GMP-AMP synthase synthesizes a cyclic dinucleotide that initiates an inflammatory cellular response. Mouse studies that recapitulate causative mutations in the autoimmune disease Aicardi-Goutières syndrome demonstrate that ablating the cyclic GMP-AMP synthase gene abolishes the deleterious phenotype. Here, we report the discovery of a class of cyclic GMP-AMP synthase inhibitors identified by a high-throughput screen. These compounds possess defined structure-activity relationships and we present crystal structures of cyclic GMP-AMP synthase, double-stranded DNA, and inhibitors within the enzymatic active site. We find that a chemically improved member, RU.521, is active and selective in cellular assays of cyclic GMP-AMP synthase-mediated signaling and reduces constitutive expression of interferon in macrophages from a mouse model of Aicardi-Goutières syndrome. RU.521 will be useful toward understanding the biological roles of cyclic GMP-AMP synthase and can serve as a molecular scaffold for development of future autoimmune therapies.Upon DNA binding cyclic GMP-AMP synthase (cGAS) produces a cyclic dinucleotide, which leads to the upregulation of inflammatory genes. Here the authors develop small molecule cGAS inhibitors, functionally characterize them and present the inhibitor and DNA bound cGAS crystal structures, which will facilitate drug development.
Topics: Animals; Autoimmune Diseases; Autoimmune Diseases of the Nervous System; Autoimmunity; Benzofurans; DNA; Enzyme Inhibitors; High-Throughput Screening Assays; Immunity, Innate; Inflammation; Macrophages; Mass Spectrometry; Mice; Nervous System Malformations; Nucleotidyltransferases; Small Molecule Libraries; Structure-Activity Relationship
PubMed: 28963528
DOI: 10.1038/s41467-017-00833-9