Dataset Information

People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR⁺ Tregs.

ABSTRACT: The importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This study aims to investigate which alterations might be present in pwPPMS free of disease-modifying drugs (DMD) in comparison to age- and sex-matched healthy controls. A multicentric cross-sectional study was performed using 23 pwPPMS and 23 healthy controls. The phenotype of conventional CD4⁺ and CD8⁺ T cells, regulatory T cells (Tregs), B cells, natural killer (NK) T cells and NK cells was assessed. Lower numbers of central memory CD4⁺ and CD8⁺ T cells and activated HLA-DR⁺ Tregs were observed in pwPPMS. Regarding NK and NKT cells, pwPPMS presented higher percentages of CD56^dimCD57⁺ NK cells expressing NKp46 and of NKT cells expressing KIR2DL2/3 and NKp30. Higher disease severity scores and an increasing time since diagnosis was correlated with lower numbers of inhibitory NK cells subsets. Our findings contribute to reinforcing the hypotheses that alterations in peripheral immune cells are present in pwPPMS and that changes in NK cell populations are the strongest correlate of disease severity.

SUBMITTER: Canto-Gomes J

PROVIDER: S-EPMC9913799 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR<sup>+</sup> Tregs.

Canto-Gomes João J Da Silva-Ferreira Sara S Silva Carolina S CS Boleixa Daniela D Martins da Silva Ana A González-Suárez Inés I Cerqueira João J JJ Correia-Neves Margarida M Nobrega Claudia C

Cells 20230129 3

The importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This study aims to investigate which alterations might be present in pwPPMS free of disease-modifying drugs (DMD) in comparison to age- and sex-matched healthy controls. A m ...[more]

PMID: 36766781

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Project description:BackgroundSustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.MethodsWe adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9-/- mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.ResultsScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DRlowS100Ahigh monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.ConclusionsThis study identifies HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.

Dataset Information

People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR⁺ Tregs.

Publications

People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR<sup>+</sup> Tregs.

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Dataset Information

People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR+ Tregs.

Publications

People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR<sup>+</sup> Tregs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR⁺ Tregs.