Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: May 22, 2020

Abstract At present, it is not clear how memory B lymphocytes are maintained over time, and whether only as circulating cells or also residing in particular tissues. Here we describe distinct populations of isotype-switched (Bsm) murine spleen bone marrow, identified according to individual transcriptional signature cell receptor repertoire. A population marginal zone-like located exclusively the spleen, while a quiescent Bsm found marrow. Three further resident populations, present represent transitional follicular B1 cells, respectively. representing 10-20% marrow one qualifying circulating. In all individually dock onto VCAM1 + stromal and, reminiscent T plasma void activation, proliferation mobility.

Language: Английский

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P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: June 20, 2019

Abstract Sepsis is characterized by a systemic inflammatory response followed immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome important for establishing an after activation purinergic P2X7 receptor. Here, we study cohort individuals intra-abdominal origin sepsis show that patient monocytes have impaired Furthermore, most sepsis-related deaths among whose profoundly altered. In from patients, receptor associated dysfunction. results damage, which turn inhibits HIF-1α. We mortality increases mouse model when activated vivo. These data reveal molecular mechanism initiated contributes to impairment during infection.

Language: Английский

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Development, application and computational analysis of high-dimensional fluorescent antibody panels for single-cell flow cytometry

Nature Protocols, Journal Year: 2019, Volume and Issue: 14(7), P. 1946 - 1969

Published: June 3, 2019

Language: Английский

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Tissue-resident memory T cells invade the brain parenchyma in multiple sclerosis white matter lesions

Brain, Journal Year: 2020, Volume and Issue: 143(6), P. 1714 - 1730

Published: March 31, 2020

Abstract Multiple sclerosis is a chronic inflammatory, demyelinating disease, although it has been suggested that in the progressive late phase, inflammatory lesion activity declines. We recently showed Netherlands Brain Bank multiple sclerosis-autopsy cohort considerable ongoing also at end stage of based on microglia/macrophage activity. have now studied role T cells this autopsy cases. quantified and perivascular T-cell cuffing standardized location medulla oblongata 146 sclerosis, 20 neurodegenerative control non-neurological brain donors. In addition, we CD3+, CD4+, CD8+ 140 subcortical white matter lesions. The either space or parenchyma was determined using CD8/laminin staining confocal imaging. Finally, analysed cells, isolated from fresh tissues lesions (n = 8), normal-appearing 7), 10), by flow cytometry. matter, number increased compared to matter. active mixed active/inactive lesions, further augmented Active were enriched for both CD4+ latter being more abundant all types. Perivascular clustering only found cases with disease course correlated higher percentage load without clusters oblongata. samples, located mostly space, whereas 16.3% encountered parenchyma. tissue-resident memory phenotype expression CD69, CD103, CD44, CD49a, PD-1 absence S1P1. They upregulated markers homing (CXCR6), reactivation (Ki-67), cytotoxicity (GPR56), yet lacked cytolytic enzyme granzyme B. These data show cases, demyelinated associated an space. Inflammatory are populated which signs infiltration

Language: Английский

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c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host–microbiota homeostasis

Nature Immunology, Journal Year: 2019, Volume and Issue: 20(4), P. 471 - 481

Published: Feb. 18, 2019

Language: Английский

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Extracellular DNA traps in inflammation, injury and healing

Nature Reviews Nephrology, Journal Year: 2019, Volume and Issue: 15(9), P. 559 - 575

Published: June 18, 2019

Language: Английский

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T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 6, 2021

Abstract Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with from those cross-reactive immunity to other coronaviruses. Here we show a range assays that differentially capture immune function characterise responses. Strong ex vivo ELISpot and proliferation multiple antigens (including M, NP ORF3) are found in 168 PCR-confirmed volunteers, but rare 119 uninfected volunteers. Highly exposed seronegative healthcare workers recent COVID-19-compatible illness response patterns characteristic infection. By contrast, >90% convalescent or unexposed cellular lactate spike subunits S1/S2, indicating pre-existing populations. The detection is therefore critically dependent on assay antigen selection. Memory specific non-spike proteins provide method distinguish infection

Language: Английский

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CyTOF® for the Masses

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 14, 2022

Mass cytometry has revolutionized immunophenotyping, particularly in exploratory settings where simultaneous breadth and depth of characterization immune populations is needed with limited samples such as preclinical clinical tumor immunotherapy. also a powerful tool for single-cell immunological assays, especially complex diverse intratumoral subsets or immunotherapeutic cell populations. Through the elimination spectral overlap seen optical flow by replacement fluorescent labels metal isotopes, mass allows, on average, robust analysis 60 individual parameters simultaneously. This is, however, associated significantly increased complexity design, execution, interpretation experiments. To address key pitfalls fragmentation, complexity, data immunologists who are novices to these techniques, we have developed comprehensive resource guide. Included this review experiment panel antibody conjugations, sample staining, acquisition, pre-processing analysis. Where feasible multiple resources same process compared, allowing researchers experienced but minimal expertise develop data-driven streamlined project workflow. It our hope that manuscript will prove useful both beginning advanced users cytometry.

Language: Английский

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Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 26(1), P. 11 - 31

Published: Aug. 21, 2024

Language: Английский

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IL-4 induces M2 macrophages to produce sustained analgesia via opioids

JCI Insight, Journal Year: 2020, Volume and Issue: 5(4)

Published: Feb. 26, 2020

IL-4 is a pleiotropic antiinflammatory cytokine, which can be neuroprotective after nervous system injury. The beneficial actions of are thought to result from the blunting action inflammatory mediators, such as proinflammatory cytokines. Here, we demonstrate that induces M2 macrophages continuously produce opioid peptides and ameliorate pain. application at injured nerves in mice shifted F4/80+ M1 phenotype, synthesized (Met-enkephalin, β-endorphin, dynorphin A 1-17). These effects were accompanied by long-lasting attenuation neuropathy-induced mechanical hypersensitivity, beyond treatment. This IL-4-induced analgesia was decreased peptide antibodies receptor (δ, μ, κ) antagonists applied nerves, confirms involvement local system. participation supported recipient injected with IL-4–treated donors. Together, IL-4–induced produced peptides, activated peripheral receptors diminish Fostering opioid-mediated intrinsic may strategy tackle pathological

Language: Английский

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