Nature reviews. Immunology, Год журнала: 2023, Номер 24(4), С. 235 - 249
Опубликована: Сен. 26, 2023
Язык: Английский
Nature Reviews Nephrology, Год журнала: 2023, Номер 19(8), С. 509 - 524
Опубликована: Май 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
Язык: Английский
Процитировано
270
Annual Review of Immunology, Год журнала: 2023, Номер 41(1), С. 533 - 560
Опубликована: Фев. 28, 2023
Autoreactive B cells and interferons are central players in systemic lupus erythematosus (SLE) pathogenesis. The partial success of drugs targeting these pathways, however, supports heterogeneity upstream mechanisms contributing to disease In this review, we focus on recent insights from genetic immune monitoring studies patients that refining our understanding basic mechanisms. Among them, novel mutations genes affecting intrinsic cell activation or clearance interferogenic nucleic acids have been described. Mitochondria emerged as relevant inducers and/or amplifiers SLE pathogenesis through a variety include disruption organelle integrity compartmentalization, defective metabolism, failure quality control measures. These result extra- intracellular release well innate adaptive activation. A classic autoantibody specificities found recapitulate alterations associated with monogenic trigger amplification loops. Finally, atypical extrafollicular T helper subsets proposed contribute the generation autoantibodies. Overall, provide opportunities deepen immunophenotypic surveillance open door patient stratification personalized, rational approaches therapy.
Язык: Английский
Процитировано
108
Annual Review of Immunology, Год журнала: 2023, Номер 41(1), С. 453 - 481
Опубликована: Фев. 8, 2023
The innate immune system detects pathogens via germline-encoded receptors that bind to conserved pathogen ligands called pathogen-associated molecular patterns (PAMPs). Here we consider an additional strategy of sensing effector-triggered immunity (ETI). ETI involves detection pathogen-encoded virulence factors, also effectors. Pathogens produce effectors manipulate hosts create a replicative niche and/or block host immunity. Unlike PAMPs, are often diverse and rapidly evolving can thus be unsuitable targets for direct by receptors. Effectors instead sensed indirectly their activities. is viable used across phyla, including plants, but the mechanisms complex compared simple receptor/ligand-based PAMP detection. survey functions ETI, with particular focus on emerging insights from animal studies. We suggest many examples may remain discovered, hiding in plain sight throughout immunology.
Язык: Английский
Процитировано
96
Nature reviews. Immunology, Год журнала: 2023, Номер 23(7), С. 453 - 471
Опубликована: Янв. 12, 2023
Язык: Английский
Процитировано
82
Biochemical Pharmacology, Год журнала: 2022, Номер 200, С. 115026 - 115026
Опубликована: Март 31, 2022
The interferon regulatory factor (IRF) family of transcription factors play a vital role in the human innate antiviral immune responses with production interferons (IFNs) as hallmark outcome activation. In recent years, IRF3 has been considered principal early regulator type I IFNs (TI-IFNs) directly downstream intracellular virus sensing. Despite decades research on IRF-activating pathways, many questions remain regulation kinases IκB kinase epsilon (IKKε) and TANK-binding kinase-1 (TBK1) scaffold proteins TRAF member-associated NF-kappa-B activator (TANK), NF-kappa-B-activating kinase-associated protein 1 (NAP1) 1-binding (TBKBP1)/similar to NAP1 TBK1 adaptor (SINTBAD) are believed be core components an IRF3-activation complex yet their contextual involvement composition still unclear. This review will give overview signaling pathways leading activation discuss developments our understanding its proximal regulation.
Язык: Английский
Процитировано
77
Nature Reviews Rheumatology, Год журнала: 2022, Номер 18(8), С. 435 - 447
Опубликована: Май 6, 2022
Язык: Английский
Процитировано
76
Current Opinion in Immunology, Год журнала: 2022, Номер 74, С. 172 - 182
Опубликована: Янв. 25, 2022
Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type IFNs SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of IFNs, proteins can inhibit various steps IFN production response. Exogenous viral growth vitro. In animal species vivo, deficiencies underlie higher loads more severe disease than control animals. The early administration exogenous improves infection control. humans, inborn errors of, auto-antibodies against life-threatening COVID-19 pneumonia. Overall, are essential for host defense individual whole organisms.
Язык: Английский
Процитировано
71
Immunity, Год журнала: 2024, Номер 57(4), С. 718 - 730
Опубликована: Апрель 1, 2024
Язык: Английский
Процитировано
62
The Journal of Experimental Medicine, Год журнала: 2023, Номер 220(3)
Опубликована: Янв. 13, 2023
The cGAS-STING pathway is an evolutionarily conserved immune signaling critical for microbial defense. Unlike other innate pathways that largely rely on stationary cascades of events, STING highly mobile in the cell. activated ER, but only signals after it arrives Golgi, and then quickly degraded by lysosome. Each step trafficking through secretory regulated host factors. Homeostatic via COPI-, COPII-, clathrin-coated vesicles important maintaining baseline tissue cellular immunity. Aberrant vesicular or lysosomal dysfunction produces signal STING, which often leads to pathology mice humans. Many trafficking-mediated diseases appear impact central nervous system, leading neurodegeneration. Therefore, introduces a new dimension likely has broad implications human disease.
Язык: Английский
Процитировано
52
Immunological Reviews, Год журнала: 2024, Номер 322(1), С. 98 - 112
Опубликована: Янв. 9, 2024
Summary Human autoantibodies (auto‐Abs) neutralizing type I IFNs were first discovered in a woman with disseminated shingles and described by Ion Gresser from 1981 to 1984. They have since been found patients diverse conditions are even used as diagnostic criterion autoimmune polyendocrinopathy syndrome 1 (APS‐1). However, their apparent lack of association viral diseases, including shingles, led wide acceptance the conclusion that they had no pathological consequences. This perception began change 2020, when underlie about 15% cases critical COVID‐19 pneumonia. shown other severe 5%, 20%, 40% influenza pneumonia, MERS West Nile virus encephalitis, respectively. also seem be associated various settings. These auto‐Abs present all age groups general population, but frequency increases reach at least 5% elderly. We estimate 100 million people worldwide carry IFNs. Here, we briefly review history study these auto‐Abs, focusing particularly on known causes
Язык: Английский
Процитировано
28