Autoimmunity and organ damage in systemic lupus erythematosus

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(6), P. 605 - 614

Published: May 4, 2020

Language: Английский

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The JAK-STAT pathway at 30: Much learned, much more to do

Cell, Journal Year: 2022, Volume and Issue: 185(21), P. 3857 - 3876

Published: Oct. 1, 2022

Language: Английский

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Human Lung Stem Cell-Based Alveolospheres Provide Insights into SARS-CoV-2-Mediated Interferon Responses and Pneumocyte Dysfunction

Cell stem cell, Journal Year: 2020, Volume and Issue: 27(6), P. 890 - 904.e8

Published: Oct. 21, 2020

Language: Английский

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Pathogenesis of autoimmune disease

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(8), P. 509 - 524

Published: May 10, 2023

Autoimmune diseases are a diverse group of conditions characterized by aberrant B cell and T reactivity to normal constituents the host. These occur widely affect individuals all ages, especially women. Among these diseases, most prominent immunological manifestation is production autoantibodies, which provide valuable biomarkers for diagnosis, classification disease activity. Although cells have key role in pathogenesis, they technically more difficult assay. In general, autoimmune results from an interplay between genetic predisposition environmental factors. Genetic autoimmunity complex can involve multiple genes that regulate function immune populations. Less frequently, result single-gene mutations regulatory pathways. Infection seems be common trigger disease, although microbiota also influence pathogenesis. As shown seminal studies, patients may express autoantibodies many years before appearance clinical or laboratory signs — period called pre-clinical autoimmunity. Monitoring autoantibody expression at-risk populations therefore enable early detection initiation therapy prevent attenuate tissue damage. Autoimmunity not static, however, remission achieved some treated with current agents. host constituents. This Review provides overview basis focus on given their as markers

Language: Английский

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Regulation of PD-L1 Expression by NF-κB in Cancer

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Nov. 25, 2020

Immune checkpoints are inhibitory receptor/ligand pairs regulating immunity that exploited as key targets of anti-cancer therapy. Although the PD-1/PD-L1 pair is one most studied immune checkpoints, several aspects its biology remain to be clarified. It has been established PD-1 an receptor up-regulated by activated T, B, and NK lymphocytes ligand PD-L1 mediates a negative feedback lymphocyte activation, contributing restoration steady state condition after acute responses. This loop might become detrimental in presence either chronic infection or growing tumor. expression tumors currently used biomarker orient therapeutic decisions; nevertheless, our knowledge about regulation limited. The present review discusses how NF-κB, master transcription factor inflammation immunity, emerging positive regulator cancer. NF-κB directly induces gene binding promoter, it can also regulate post-transcriptionally through indirect pathways. These processes, which under conditions cellular stress drive tissue homeostasis promote healing, largely dysregulated tumors. Up-regulation cancer cells controlled via downstream signals, including oncogene- stress-induced pathways, inflammatory cytokines, chemotherapeutic drugs. Notably, shared signaling pathway epithelial cancers both epithelial-mesenchymal transition, suggesting part remodeling program. Furthermore, tumor infiltrating myeloid contribute suppressive features environment. A better understanding interplay between highly relevant

Language: Английский

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Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(5), P. 274 - 288

Published: Oct. 18, 2022

Language: Английский

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Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 91, P. 740 - 755

Published: Oct. 8, 2020

Central nervous system (CNS) innate immunity plays essential roles in infections, neurodegenerative diseases, and brain or spinal cord injuries. Astrocytes microglia are the principal cells that mediate CNS. Pattern recognition receptors (PRRs), expressed by astrocytes microglia, sense pathogen-derived endogenous ligands released damaged initiate immune response. Toll-like (TLRs) a well-characterized family of PRRs. The contribution microglial TLR signaling to CNS pathology has been extensively investigated. Even though assume wide variety key functions, information about role astroglial TLRs disease injuries is limited. Because display heterogeneity exhibit phenotypic plasticity depending on effectors present local milieu, they can exert both detrimental beneficial effects. modulators these paradoxical properties. goal current review highlight played diseases. We discuss host defense as well dissemination viral bacterial infections examine link between pathogenesis diseases evidence showing pivotal influence sterile inflammation injury. Finally, we define research questions areas warrant further investigations context astrocytes, TLRs, dysfunction.

Language: Английский

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The interaction between ferroptosis and inflammatory signaling pathways

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 21, 2023

Abstract Ferroptosis is an iron-dependent regulated cell death driven by excessive lipid peroxidation. Inflammation one common and effective physiological event that protects against various stimuli to maintain tissue homeostasis. However, the dysregulation of inflammatory responses can cause imbalance immune system, dysfunction death. Recent studies have pointed out activation inflammation, including multiple inflammation-related signaling pathways, lead ferroptosis. Among related signal transduction we focused on five classical namely, JAK-STAT, NF-κB, inflammasome, cGAS-STING MAPK expounded their roles in To date, many agents shown therapeutic effects ferroptosis-related diseases modulating aforementioned pathways vivo vitro. Moreover, regulatory these iron metabolism peroxidation been described detail, contributing further understanding pathophysiological process Taken together, targeting inflammation will provide appropriate ways intervene ferroptosis diseases.

Language: Английский

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Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 19, 2023

Abstract The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism transmembrane transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, other specific molecules activate JAK-STAT signaling drive a series physiological pathological processes, including proliferation, metabolism, immune response, inflammation, malignancy. Dysregulated related genetic mutations are strongly associated activation cancer progression. Insights into structures functions have led development approval diverse drugs for clinical treatment diseases. Currently, been developed mainly target commonly divided three subtypes: cytokine or receptor antibodies, JAK inhibitors, STAT inhibitors. And novel agents also continue be tested in preclinical studies. effectiveness safety each kind drug warrant further scientific trials before put being applications. Here, we review current understanding fundamental composition function pathway. We discuss advancements JAK-STAT–related pathogenic mechanisms; targeted therapies various diseases, especially disorders, cancers; newly inhibitors; challenges directions field.

Language: Английский

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IFN-γ and TNF-α drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 lungs and inflammatory diseases with tissue inflammation

Genome Medicine, Journal Year: 2021, Volume and Issue: 13(1)

Published: April 20, 2021

Abstract Background Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 other inflammatory diseases established therapies help nominate immunomodulatory therapies. Methods To identify cellular phenotypes that be across tissues affected by disparate diseases, we developed meta-analysis integration pipeline models removes effects of technology, tissue origin, donor confound cell-type identification. Using this approach, integrated > 300,000 single-cell transcriptomic profiles from COVID-19-affected lungs healthy subjects five diseases: rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), interstitial lung disease. We tested association severe/inflamed status compared to control using mixed-effects modeling. define environmental factors within these shape macrophage phenotypes, stimulated human blood-derived macrophages defined combinations factors, emphasizing in particular antiviral interferons IFN-beta (IFN-β) IFN-gamma (IFN-γ), pro-inflammatory cytokines such as TNF. Results built an reference consisting 125 or disease-affected donors diseases. observed CXCL10+ CCL2+ state is strikingly abundant severe bronchoalveolar lavage samples, inflamed RA synovium, CD ileum, UC colon. These cells exhibited distinct arrangement interferon response genes, including elevated levels CXCL10 , CXCL9 CCL2 CCL3 GBP1, STAT1 IL1B . Further, found phenotype induced upon co-stimulation IFN-γ TNF-α. Conclusions Our integrative analysis identified study supports key role together TNF-α driving lungs, well colon, which targeted existing

Language: Английский

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