RNA modifications: importance in immune cell biology and related diseases

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Сен. 22, 2022

RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.

Язык: Английский

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γδ T cells: origin and fate, subsets, diseases and immunotherapy

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 22, 2023

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering use allogeneic Vδ2

Язык: Английский

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The Role of Viral Infections in the Onset of Autoimmune Diseases

Viruses, Год журнала: 2023, Номер 15(3), С. 782 - 782

Опубликована: Март 18, 2023

Autoimmune diseases (AIDs) are the consequence of a breach in immune tolerance, leading to inability sufficiently differentiate between self and non-self. Immune reactions that targeted towards self-antigens can ultimately lead destruction host’s cells development autoimmune diseases. Although disorders comparatively rare, worldwide incidence prevalence is increasing, they have major adverse implications for mortality morbidity. Genetic environmental factors thought be contributing autoimmunity. Viral infections one triggers Current research suggests several mechanisms, such as molecular mimicry, epitope spreading, bystander activation, cause viral-induced Here we describe latest insights into pathomechanisms discuss recent findings on COVID-19 AIDs.

Язык: Английский

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Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations

Nature, Год журнала: 2024, Номер 625(7994), С. 321 - 328

Опубликована: Янв. 10, 2024

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that most prevalent in Northern Europe. Although it known inherited risk for MS located within or close proximity to immune-related genes, unknown when, where how this genetic originated

Язык: Английский

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CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis

Med, Год журнала: 2024, Номер 5(6), С. 550 - 558.e2

Опубликована: Март 29, 2024

BackgroundProgressive multiple sclerosis (MS) is characterized by compartmentalized smoldering neuroinflammation caused the proliferation of immune cells residing in central nervous system (CNS), including B cells. Although inflammatory activity can be prevented immunomodulatory therapies during early disease, such typically fail to halt disease progression. CD19 chimeric antigen receptor (CAR)-T cell have revolutionized field hematologic malignancies. generally considered efficacious, serious adverse events associated with CAR-T as effector cell-associated neurotoxicity syndrome (ICANS) been observed. Successful use rheumatic diseases like systemic lupus erythematosus and neuroimmunological myasthenia gravis recently observed, suggesting possible application other autoimmune diseases.MethodsHere, we report first individual treatment a fully human therapy (KYV-101) two patients progressive MS.FindingsCD19 administration resulted acceptable safety profiles for both patients. No ICANS was observed despite detection cerebrospinal fluid. In case 1, intrathecal antibody production fluid decreased notably after infusion sustained through day 64.ConclusionsCD19 MS an profile. presence expansion were without clinical signs neurotoxicity, which, along reduction, indicates expansion-dependent effects on CD19+ target CNS. Larger studies assessing are warranted.FundingBoth treatments well generated data not based external funding.

Язык: Английский

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Mesenchymal stem cell secretome and extracellular vesicles for neurodegenerative diseases: Risk-benefit profile and next steps for the market access

Bioactive Materials, Год журнала: 2023, Номер 29, С. 16 - 35

Опубликована: Июнь 28, 2023

Neurodegenerative diseases represent a growing burden on healthcare systems worldwide. Mesenchymal stem cells (MSCs) have shown promise as potential therapy due to their neuroregenerative, neuroprotective, and immunomodulatory properties, which are, however, linked the bioactive substances they release, collectively known secretome. This paper provides an overview of most recent research safety efficacy MSC-derived secretome extracellular vesicles (EVs) in clinical (if available) preclinical models Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis, multiple Huntington's acute ischemic stroke, spinal cord injury. The article explores biologically active within MSC-secretome/EVs, mechanisms responsible for observed therapeutic effects, strategies that may be used optimize MSC-secretome/EVs production based specific needs. review concludes with critical discussion current trials perspective future directions translating MSC-secretome EVs into clinic, specifically regarding how address challenges associated pharmaceutical manufacturing, including scalability, batch-to-batch consistency, adherence Good Manufacturing Practices (GMP) guidelines, formulation, storage, along quality controls, access market relative costs, value money impact total expenditure.

Язык: Английский

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The immunopathogenesis of narcolepsy type 1

Nature reviews. Immunology, Год журнала: 2023, Номер 24(1), С. 33 - 48

Опубликована: Июль 3, 2023

Язык: Английский

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Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Окт. 30, 2023

Sensitive and reliable protein biomarkers are needed to predict disease trajectory personalize treatment strategies for multiple sclerosis (MS). Here, we use the highly sensitive proximity-extension assay combined with next-generation sequencing (Olink Explore) quantify 1463 proteins in cerebrospinal fluid (CSF) plasma from 143 people early-stage MS 43 healthy controls. With longitudinally followed discovery replication cohorts, identify CSF that consistently predicted both short- long-term progression. Lower levels of neurofilament light chain (NfL) is superior predicting absence activity two years after sampling (replication AUC = 0.77) compared all other tested proteins. Importantly, also a combination 11 (CXCL13, LTA, FCN2, ICAM3, LY9, SLAMF7, TYMP, CHI3L1, FYB1, TNFRSF1B NfL) severity disability worsening according normalized age-related score 0.90). The identification these may help elucidate pathogenetic processes might aid decisions on persons MS.

Язык: Английский

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The neuropathobiology of multiple sclerosis

Nature reviews. Neuroscience, Год журнала: 2024, Номер 25(7), С. 493 - 513

Опубликована: Май 24, 2024

Язык: Английский

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STING orchestrates the neuronal inflammatory stress response in multiple sclerosis

Cell, Год журнала: 2024, Номер 187(15), С. 4043 - 4060.e30

Опубликована: Июнь 14, 2024

Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce stimulator interferon genes (STING). However, activation STING requires detachment from stromal interaction molecule 1 (STIM1), process triggered by glutamate excitotoxicity. This initiates non-canonical signaling, which leads to autophagic degradation glutathione peroxidase 4 (GPX4), essential for redox homeostasis thereby inducing ferroptosis. Both genetic pharmacological interventions target protect against inflammation-induced neurodegeneration. Our findings position as central regulator detrimental integrating inflammation with signaling cause cell death, present it tractable treating MS.

Язык: Английский

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