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Frontiers in Immunology 2022
Topics: Humans; Antigen Presentation; Autoimmunity; Aminopeptidases; Immune System Diseases
PubMed: 36311705
DOI: 10.3389/fimmu.2022.1055152 -
Cell Research Feb 2023Autoimmunity and autoinflammation arise from aberrant immunological and inflammatory responses toward self-components, contributing to various autoimmune diseases and... (Review)
Review
Autoimmunity and autoinflammation arise from aberrant immunological and inflammatory responses toward self-components, contributing to various autoimmune diseases and autoinflammatory diseases. RNA-binding proteins (RBPs) are essential for immune cell development and function, mainly via exerting post-transcriptional regulation of RNA metabolism and function. Functional dysregulation of RBPs and abnormities in RNA metabolism are closely associated with multiple autoimmune or autoinflammatory disorders. Distinct RBPs play critical roles in aberrant autoreactive inflammatory responses via orchestrating a complex regulatory network consisting of DNAs, RNAs and proteins within immune cells. In-depth characterizations of RBP-RNA interactomes during autoimmunity and autoinflammation will lead to a better understanding of autoimmune pathogenesis and facilitate the development of effective therapeutic strategies. In this review, we summarize and discuss the functions of RBP-RNA interactions in controlling aberrant autoimmune inflammation and their potential as biomarkers and therapeutic targets.
Topics: Humans; Autoimmunity; RNA; Autoimmune Diseases; Gene Expression Regulation; Inflammation
PubMed: 36599968
DOI: 10.1038/s41422-022-00752-5 -
Autophagy Feb 2021IRGM is a genetic risk factor for several autoimmune diseases. However, the mechanism of IRGM-mediated protection in autoimmunity remains undetermined. The abnormal... (Review)
Review
IRGM is a genetic risk factor for several autoimmune diseases. However, the mechanism of IRGM-mediated protection in autoimmunity remains undetermined. The abnormal activation of type I interferon (IFN) response is one of the significant factors in the pathogenesis of several autoimmune diseases. In our recent study, we showed that IRGM is a master suppressor of the interferon response. We found that the depletion of IRGM results in constitutively activated CGAS-STING1, DDX58/RIG-I-MAVS, and TLR3-TICAM1/TRIF signaling pathways resulting in upregulation of almost all IFN-responsive genes. Mechanistically, IRGM utilizes a two-pronged mechanism to suppress the interferon response. First, it mediates SQSTM1/p62-dependent selective macroautophagy/autophagy of nucleic acid sensor proteins, including CGAS, DDX58/RIG-I, and TLR3. Second, it facilitates the removal of defective mitochondria by mitophagy and avoids a buildup of mito-ROS and mito-damage/danger-associated molecular patterns (DAMPs). Thus, IRGM deficiency results in increased nucleic acid sensors and DAMPs engaging a vicious cycle of aberrant activation of IFN response that is known to occur in systemic autoimmune-like conditions.
Topics: Autoimmune Diseases; Autoimmunity; Autophagy; GTP-Binding Proteins; Humans; Mitochondria; Signal Transduction
PubMed: 32813580
DOI: 10.1080/15548627.2020.1810920 -
Journal of Autoimmunity May 2023Immune aging is a complex process rendering the host susceptible to cancer, infection, and insufficient tissue repair. Many autoimmune diseases preferentially occur... (Review)
Review
Immune aging is a complex process rendering the host susceptible to cancer, infection, and insufficient tissue repair. Many autoimmune diseases preferentially occur during the second half of life, counterintuitive to the concept of excess adaptive immunity driving immune-mediated tissue damage. T cells are particularly susceptible to aging-imposed changes, as they are under extreme proliferative pressure to fulfill the demands of clonal expansion and of homeostatic T cell repopulation. T cells in older adults have a footprint of genetic and epigenetic changes, lack mitochondrial fitness, and fail to maintain proteostasis, diverging them from host protection to host injury. Here, we review recent progress in understanding how the human T-cell system ages and the evidence detailing how T cell aging contributes to autoimmune conditions. T cell aging is now recognized as a risk determinant in two prototypic autoimmune syndromes; rheumatoid arthritis and giant cell arteritis. The emerging concept adds susceptibility to autoimmune and autoinflammatory disease to the spectrum of aging-imposed adaptations and opens new opportunities for immunomodulatory therapy by restoring the functional intactness of aging T cells.
Topics: Humans; Aged; Autoimmunity; T-Lymphocytes; Autoimmune Diseases; Aging; Cellular Senescence; Risk Factors
PubMed: 36357240
DOI: 10.1016/j.jaut.2022.102947 -
The Journal of Investigative Dermatology Mar 2022T cells are key drivers of autoimmunity in numerous noncommunicable inflammatory skin diseases by directly harming host tissue or through helping B cells in producing... (Review)
Review
T cells are key drivers of autoimmunity in numerous noncommunicable inflammatory skin diseases by directly harming host tissue or through helping B cells in producing autoantibodies. Technological advances have contributed to identifying autoantigens, the Holy Grail of autoimmunity, in many inflammatory disorders of the skin. Novel therapeutic approaches such as chimeric (auto)antibody receptor T cells are a milestone on the way to finding individualized, well-tolerated, targeted therapies. This review summarizes the current knowledge on pathogenesis, immune response pattern‒related ontology, diagnostic approaches, and treatment options of autoimmune skin diseases.
Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmunity; Humans; T-Lymphocytes
PubMed: 34538423
DOI: 10.1016/j.jid.2021.04.032 -
Frontiers in Immunology 2022The complement system (CS) is an ancient and highly conserved part of the innate immune system with important functions in immune defense. The multiple fragments bind to... (Review)
Review
The complement system (CS) is an ancient and highly conserved part of the innate immune system with important functions in immune defense. The multiple fragments bind to specific receptors on innate and adaptive immune cells, the activation of which translates the initial humoral innate immune response (IR) into cellular innate and adaptive immunity. Dysregulation of the CS has been associated with the development of several autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ANCA-associated vasculitis, and autoimmune bullous dermatoses (AIBDs), where complement drives the inflammatory response in the effector phase. The role of the CS in autoimmunity is complex. On the one hand, complement deficiencies were identified as risk factors to develop autoimmune disorders. On the other hand, activation of complement can drive autoimmune responses. The anaphylatoxins C3a and C5a are potent mediators and regulators of inflammation during the effector phase of autoimmunity through engagement of specific anaphylatoxin receptors, i.e., C3aR, C5aR1, and C5aR2 either on or in immune cells. In addition to their role in innate IRs, anaphylatoxins regulate humoral and cellular adaptive IRs including B-cell and T-cell activation, differentiation, and survival. They regulate B- and T-lymphocyte responses either directly or indirectly through the activation of anaphylatoxin receptors dendritic cells that modulate lymphocyte function. Here, we will briefly review our current understanding of the complex roles of anaphylatoxins in the regulation of immunologic tolerance and the early events driving autoimmunity and the implications of such regulation for therapeutic approaches that target the CS.
Topics: Anaphylatoxins; Autoimmune Diseases; Autoimmunity; Complement System Proteins; Humans; T-Lymphocytes
PubMed: 35958588
DOI: 10.3389/fimmu.2022.958392 -
Frontiers in Immunology 2022
Topics: Autoimmunity; Complement System Proteins
PubMed: 36466859
DOI: 10.3389/fimmu.2022.1085525 -
Frontiers in Immunology 2022Autoimmune disease results from the immune response against self-antigens, while cancer develops when the immune system does not respond to malignant cells. Thus, for... (Review)
Review
Autoimmune disease results from the immune response against self-antigens, while cancer develops when the immune system does not respond to malignant cells. Thus, for years, autoimmunity and cancer have been considered as two separate fields of research that do not have a lot in common. However, the discovery of immune checkpoints and the development of anti-cancer drugs targeting PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways proved that studying autoimmune diseases can be extremely helpful in the development of novel anti-cancer drugs. Therefore, autoimmunity and cancer seem to be just two sides of the same coin. In the current review, we broadly discuss how various regulatory cell populations, effector molecules, genetic predisposition, and environmental factors contribute to the loss of self-tolerance in autoimmunity or tolerance induction to cancer. With the current paper, we also aim to convince the readers that the pathways involved in cancer and autoimmune disease development consist of similar molecular players working in opposite directions. Therefore, a deep understanding of the two sides of immune tolerance is crucial for the proper designing of novel and selective immunotherapies.
Topics: Antineoplastic Agents; Autoimmune Diseases; Autoimmunity; Humans; Immunotherapy; Neoplasms
PubMed: 35634292
DOI: 10.3389/fimmu.2022.793234 -
Frontiers in Immunology 2022Various immune cell types, including monocytes, macrophages, and adaptive immune T and B cells, play major roles in inflammation in systemic autoimmune diseases.... (Review)
Review
Various immune cell types, including monocytes, macrophages, and adaptive immune T and B cells, play major roles in inflammation in systemic autoimmune diseases. However, the precise contribution of these cells to autoimmunity remains elusive. Transcriptome analysis has added a new dimension to biology and medicine. It enables us to observe the dynamics of gene expression in different cell types in patients with diverse diseases as well as in healthy individuals, which cannot be achieved with genomic information alone. In this review, we summarize how transcriptome analysis has improved our understanding of the pathological roles of immune cells in autoimmune diseases with a focus on the ImmuNexUT database we reported. We will also discuss the common experimental and analytical design of transcriptome analyses. Recently, single-cell RNA-seq analysis has provided atlases of infiltrating immune cells, such as pro-inflammatory monocytes and macrophages, peripheral helper T cells, and age or autoimmune-associated B cells in various autoimmune disease lesions. With the integration of genomic data, expression quantitative trait locus (eQTL) analysis can help identify candidate causal genes and immune cells. Finally, we also mention how the information obtained from these analyses can be used practically to predict patient prognosis.
Topics: Autoimmune Diseases; Autoimmunity; Gene Expression Profiling; Humans; Inflammation; Monocytes
PubMed: 35663941
DOI: 10.3389/fimmu.2022.857269 -
Archives of Medical Research Oct 2021Virus infection can alter immune regulatory activity, and thus may be involved in the occurrence of autoimmune diseases. Recently, the pandemic of COVID-19 has posed a... (Review)
Review
Virus infection can alter immune regulatory activity, and thus may be involved in the occurrence of autoimmune diseases. Recently, the pandemic of COVID-19 has posed a huge threat to public health and emerging evidence suggests that coronavirus may be implicated in the development and pathogenesis of autoimmune diseases. However, how coronavirus infection impacts the risk of autoimmune disease remains largely unknown. In this review, we focused on the association between coronavirus and autoimmunity, and elucidated the molecular mechanisms linking coronavirus exposure to autoimmunity. Additionally, we briefly introduced the role that coronavirus plays in several autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and idiopathicthrombocytopenic purpura (ITP).
Topics: Autoimmune Diseases; Autoimmunity; COVID-19; Humans; Lupus Erythematosus, Systemic; SARS-CoV-2
PubMed: 33875273
DOI: 10.1016/j.arcmed.2021.03.012