Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(3), P. 516 - 528
Published: Feb. 23, 2023
Language: Английский
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13
Published: Sept. 23, 2022
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction myelin sheath structure. The loss leads to damage neuron’s axon and cell body, which identified as brain lesions on magnetic resonance image (MRI). pathogenesis MS remains largely unknown. However, immune mechanisms, especially those linked aberrant lymphocyte activity, are mainly responsible for neuronal damage. Th1 Th17 populations lymphocytes were primarily associated with pathogenesis. These essential differentiation encephalitogenic CD8 + T crossing blood barrier targeting in CNS. B-lymphocytes could also contribute producing anti-myelin basic protein antibodies. In later studies, function Treg Th9 cells was contributing MS. This review summarizes count lymphocyte, contributions these mechanisms Additionally, we have outlined novel therapeutics aimed amend or counts lymphocytes.
Language: Английский
Citations
81
The Lancet Neurology, Journal Year: 2023, Volume and Issue: 22(4), P. 338 - 349
Published: Feb. 7, 2023
Language: Английский
Citations
73
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: June 5, 2023
B cells occupy a vital role in the functioning of immune system, working tandem with T to either suppress or promote tumor growth within microenvironment(TME). In addition direct cell-to-cell communication, and other release exosomes, small membrane vesicles ranging size from 30-150 nm, that facilitate intercellular signaling. Exosome research is an important development cancer research, as they have been shown carry various molecules such major histocompatibility complex(MHC) integrins, which regulate TME. Given close association between TME development, targeting substances has emerged promising strategy for therapy. This review aims present comprehensive overview contributions made by exosomes microenvironment (TME). Additionally, we delve into potential cell-derived progression cancer.
Language: Английский
Citations
52
EBioMedicine, Journal Year: 2023, Volume and Issue: 94, P. 104701 - 104701
Published: July 10, 2023
Chronic active lesions (CAL) in multiple sclerosis (MS) have been observed even patients taking high-efficacy disease-modifying therapy, including B-cell depletion. Given that CAL are a major determinant of clinical progression, progression independent relapse activity (PIRA), understanding the predicted and real-world effects targeting specific lymphocyte populations is critical for designing next-generation treatments to mitigate chronic inflammation MS.We analyzed published single-cell transcriptomes from MS bioinformatically depleting subpopulations (including CD20 B-cells) via gene-regulatory-network machine-learning analysis. Motivated by results, we performed vivo MRI assessment PRL changes 72 adults with MS, 46 treated anti-CD20 antibodies 26 untreated, over ∼2 years.Although only 4.3% lymphocytes were B-cells, their depletion affect microglial genes involved iron/heme metabolism, hypoxia, antigen presentation. In vivo, tracking 202 (150 treated) 175 non-PRL (124 treated), none paramagnetic rims disappeared at follow-up, nor was there treatment effect on lesion volume, magnetic susceptibility, or T1 time. PIRA occurred 20% patients, more frequently those ≥4 (p = 0.027).Despite microglia-mediated inflammatory networks iron therapies do not fully resolve after 2-year follow up. Limited tissue turnover inefficient passage across blood-brain-barrier, paucity B-cells could explain our findings.Intramural Research Program NINDS, NIH; NINDS grants R01NS082347 R01NS082347; Dr. Miriam Sheldon G. Adelson Medical Foundation; Cariplo Foundation (grant #1677), FRRB Early Career Award #1750327); Fund Scientific (FNRS).
Language: Английский
Citations
45
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: Oct. 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.
Language: Английский
Citations
45
Annals of Neurology, Journal Year: 2024, Volume and Issue: 96(1), P. 1 - 20
Published: April 3, 2024
Clinical, pathological, and imaging evidence in multiple sclerosis (MS) suggests that a smoldering inflammatory activity is present from the earliest stages of disease underlies progression disability, which proceeds relentlessly independently clinical radiological relapses (PIRA). The complex system pathological events driving "chronic" worsening likely linked with early accumulation compartmentalized inflammation within central nervous as well insufficient repair phenomena mitochondrial failure. These mechanisms are partially lesion-independent differ those causing formation new focal demyelinating lesions; they lead to neuroaxonal dysfunction death, myelin loss, glia alterations, finally, neuronal network outweighing (CNS) compensatory mechanisms. This review aims provide an overview state art neuropathological, immunological, knowledge about underlying activity, focusing on possible biomarkers their translation into practice. ANN NEUROL 2024;96:1-20.
Language: Английский
Citations
30
The Lancet Neurology, Journal Year: 2024, Volume and Issue: 23(6), P. 615 - 624
Published: May 15, 2024
Language: Английский
Citations
22
Immunity, Journal Year: 2021, Volume and Issue: 54(12), P. 2784 - 2794.e6
Published: Oct. 9, 2021
Language: Английский
Citations
87
Journal of Neurology, Journal Year: 2021, Volume and Issue: 269(3), P. 1316 - 1334
Published: Aug. 11, 2021
Language: Английский
Citations
86
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12
Published: Feb. 1, 2022
Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which mediated by an abnormal immune response coordinated T and B cells resulting in areas of inflammation, demyelination, axonal loss. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggression but ineffective many patients. Autologous hematopoietic stem cell transplantation (HSCT) has been used as treatment patients with highly active disease, achieving long-term clinical remission most. The rationale intervention eradicate autoreactive lympho-ablative regimens restore tolerance. Immunological studies have demonstrated that autologous HSCT induces renewal TCR repertoires, resurgence regulatory cells, depletion proinflammatory subsets, suggesting “resetting” immunological memory. Although our understanding effects progressed, further work required characterize mechanisms underlie efficacy. Considering memory disease-promoting stem-like multipotent progenitors involved self-regeneration effector investigating reconstitution compartment subsets following could elucidate those mechanisms. Since all subjects need be optimally protected from vaccine-preventable diseases (including COVID-19), there ensure vaccination undergoing effective safe. Additionally, study HSCT-treated means evaluating responses distinguish broad immunosuppression resetting.
Language: Английский
Citations
48