Transforming the understanding of brain immunity

Science, Год журнала: 2023, Номер 380(6640)

Опубликована: Апрель 6, 2023

Contemporary studies have completely changed the view of brain immunity from envisioning as isolated and inaccessible to peripheral immune cells an organ in close physical functional communication with system for its maintenance, function, repair. Circulating reside special niches brain's borders, choroid plexus, meninges, perivascular spaces, which they patrol sense a remote manner. These niches, together meningeal lymphatic skull microchannels, provide multiple routes interaction between system, addition blood vasculature. In this Review, we describe current ideas about their implications aging, diseases, immune-based therapeutic approaches.

Язык: Английский

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Cellular senescence, DNA damage, and neuroinflammation in the aging brain

Trends in Neurosciences, Год журнала: 2024, Номер 47(6), С. 461 - 474

Опубликована: Май 9, 2024

Язык: Английский

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Peripheral nervous system microglia-like cells regulate neuronal soma size throughout evolution

Cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Skull bone marrow channels as immune gateways to the central nervous system

Nature Neuroscience, Год журнала: 2023, Номер 26(12), С. 2052 - 2062

Опубликована: Ноя. 23, 2023

Язык: Английский

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Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis

Immunity, Год журнала: 2023, Номер 56(7), С. 1502 - 1514.e8

Опубликована: Май 8, 2023

Язык: Английский

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The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis

Cell Reports, Год журнала: 2023, Номер 42(8), С. 113005 - 113005

Опубликована: Авг. 1, 2023

The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities CD4+ T cells in spinal cord their counterparts small intestine. Furthermore, unveil a synergistic relationship microbiota, particularly enriched with tryptophan metabolism gene EC:1.13.11.11, intestinal cells. This symbiotic collaboration results biosynthesis kynurenic acid (KYNA), which modulates recruitment aggregation GPR35-positive macrophages. Subsequently, robust helper 17 (Th17) immune response is activated, ultimately triggering EAE. Conversely, modulating KYNA-mediated GPR35 signaling Cx3cr1+ macrophages leads to amelioration These findings shed light on crucial role microbial-derived metabolites regulating responses within extraintestinal tissues.

Язык: Английский

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Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 2, 2024

Abstract Mast cells are phenotypically and functionally heterogeneous, their state is possibly controlled by local microenvironment. Therefore, specific analyses needed to understand whether mast function as powerful participants or dispensable bystanders in diseases. Here, we show that degranulation of inflammatory synovial tissues patients with rheumatoid arthritis (RA) induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), the expression MHC class II costimulatory molecules on upregulated. Collagen-induced mice treated a combination anti-IL-17A cromolyn sodium, cell membrane stabilizer, significantly reduced clinical severity decreased bone erosion. The findings present study suggest microenvironment-influenced contribute disease progression may provide further cell-targeting therapy for RA.

Язык: Английский

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Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 4, 2024

Autoimmune disorders are characterized by aberrant T cell and B reactivity to the body's own components, resulting in tissue destruction organ dysfunction. diseases affect a wide range of people many parts world have become one major concerns public health. In recent years, there been substantial progress our understanding epidemiology, risk factors, pathogenesis mechanisms autoimmune diseases. Current approved therapeutic interventions for mainly non-specific immunomodulators may cause broad immunosuppression that leads serious adverse effects. To overcome limitations immunosuppressive drugs treating diseases, precise target-specific strategies urgently needed. date, significant advances made immune tolerance, offering new avenue developing antigen-specific immunotherapies These approaches shown great potential various preclinical animal models recently evaluated clinical trials. This review describes common manifestation with focus on typical including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, sjögren's syndrome. We discuss current therapeutics developed this field, highlight use nanomaterials mRNA vaccine techniques induce tolerance.

Язык: Английский

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Single-cell RNA sequencing in donor and end-stage heart failure patients identifies NLRP3 as a therapeutic target for arrhythmogenic right ventricular cardiomyopathy

BMC Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 8, 2024

Abstract Background Dilation may be the first right ventricular change and accelerates progression of threatening tachyarrhythmias heart failure for patients with arrhythmogenic cardiomyopathy (ARVC), but treatment dilation remains limited. Methods Single-cell RNA sequencing (scRNA-seq) blood biventricular myocardium from 8 study participants was performed, including 6 end-stage ARVC 2 normal controls. ScRNA-seq data then deeply analyzed, cluster annotation, cellular proportion calculation, characterization developmental trajectories interactions. An integrative analysis our single-cell published genome-wide association study-based provided insights into cell-specific contributions to cardiac arrhythmia phenotype ARVC. Desmoglein (Dsg2) mut/mut mice were used as model verify therapeutic effects pharmacological intervention on identified cluster. Results Right ventricle enriched CCL3 + proinflammatory macrophages TNMD fibroblasts. Fibroblasts preferentially affected in perturbations associated overlap those reside genetic variants arrhythmia. Proinflammatory strongly interact fibroblast. Pharmacological inhibition Nod-like receptor protein 3 (NLRP3), a transcriptional factor predominantly expressed by several other myeloid subclusters, could significantly alleviate dysfunction Dsg2 (an mouse model). Conclusions This comprehensive lineage-specific changes at resolution. NLRP3 prevent

Язык: Английский

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Structural characterization of Russula griseocarnosa polysaccharide and its improvement on hematopoietic function

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 263, С. 130355 - 130355

Опубликована: Фев. 22, 2024

Язык: Английский

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