IL-10-providing B cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity

Geladaris, Anastasia; Häusser‐Kinzel, Silke; Pretzsch, Roxanne; Nissimov, Nitzan; Lehmann‐Horn, Klaus; Häusler, Darius; Weber, Martin

doi:10.1007/s00401-023-02552-6

Cited by 7 publications

(4 citation statements)

References 42 publications

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“…To confirm changes in TNFα expression at the protein level, we enriched CD14 + or CD16 + monocytes from cryopreserved PBMCs and showed that LPS-stimulated monocytes from MS patients expressed more TNFα post B cell depletion (Fig 5d). Increases of TNFα production by LPS-stimulated CD14 + cells was similarly observed in MS patients treated with ocrelizumab by another group 30 . However, there was no significant difference in TNFα ELISA using culture supernatant (data not shown).…”

Section: Resultsmentioning

confidence: 58%

Systems Analysis of Immune Changes after B-cell Depletion in Autoimmune Multiple Sclerosis

Wei,

Moon,

Yasumizu

et al. 2024

Preprint

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Multiple sclerosis (MS) is a complex genetically mediated autoimmune disease of the central nervous system where anti-CD20-mediated B cell depletion is remarkably effective in the treatment of early disease. While previous studies investigated the effect of B cell depletion on select immune cell subsets using flow cytometry-based methods, the therapeutic impact on patient immune landscape is unknown. In this study, we explored how a therapy-driven "in vivo perturbation" modulates the diverse immune landscape by measuring transcriptomic granularity with single-cell RNA sequencing (scRNAseq). We demonstrate that B cell depletion leads to cell type-specific changes in the abundance and function of CSF macrophages and peripheral blood monocytes. Specifically, a CSF-specific macrophage population with an anti-inflammatory transcriptomic signature and peripheral CD16+ monocytes increased in frequency post-B cell depletion. In addition, we observed increases in TNFa messenger RNA and protein in monocytes post-B cell depletion, consistent with the finding that anti-TNFa treatment exacerbates autoimmune activity in MS. In parallel, B cell depletion also induced changes in peripheral CD4+ T cell populations, including increases in the frequency of TIGIT+ regulatory T cells and marked decreases in the frequency of myelin peptide loaded-tetramer binding CD4+ T cells. Collectively, this study provides an exhaustive transcriptomic map of immunological changes, revealing different mechanisms of action contributing to the high efficacy in B cell depletion treatment of MS.

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Section: Resultsmentioning

confidence: 58%

Systems Analysis of Immune Changes after B-cell Depletion in Autoimmune Multiple Sclerosis

Wei,

Moon,

Yasumizu

et al. 2024

Preprint

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“…On the other hand, differentiation into B cells play a role in protecting the body from pathogens such as bacteria and viruses by producing antibodies and presenting antigens, but some B cells suppress autoimmune diseases by producing the inhibitory cytokine IL-10. These IL-10-producing B cells, called regulatory B cells, suppress inflammatory responses in experimental mouse models of autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis [31][32][33]. Since CD-1d-expressing CD5-positive B cells in spleen suppress various autoimmune diseases when administered to mice, and produce IL-10 when stimulated in vitro, these CD-1d-high CD5+ B cells are thought to be the major regulatory B cells.…”

Section: A Group Of B Cells Called Plasmablasts Control Encephalomyel...mentioning

confidence: 99%

Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells

Matsuzaka,

Yashiro

2023

Biologics

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, characterized by multiple lesions occurring temporally and spatially. Additionally, MS is a disease that predominates in the white population. In recent years, there has been a rapid increase in the number of patients, and it often occurs in young people, with an average age of onset of around 30 years old, but it can also occur in children and the elderly. It is more common in women than men, with a male-to-female ratio of approximately 1:3. As the immunopathogenesis of MS, a group of B cells called plasmablasts controls encephalomyelitis via IL-10 production. These IL-10-producing B cells, called regulatory B cells, suppress inflammatory responses in experimental mouse models of autoimmune diseases including MS. Since it has been clarified that these regulatory B cells are plasmablasts, it is expected that the artificial control of plasmablast differentiation will lead to the development of new treatments for MS. Among CD8-positive T cells in the peripheral blood, the proportion of PD-1-positive cells is decreased in MS patients compared with healthy controls. The dysfunction of inhibitory receptors expressed on T cells is known to be the core of MS immunopathology and may be the cause of chronic persistent inflammation. The PD-1+ CD8+ T cells may also serve as indicators that reflect the condition of each patient in other immunological neurological diseases such as MS. Th17 cells also regulate the development of various autoimmune diseases, including MS. Thus, the restoration of weakened immune regulatory functions may be a true disease-modifying treatment. So far, steroids and immunosuppressants have been the mainstream for autoimmune diseases, but the problem is that this kills not only pathogenic T cells, but also lymphocytes, which are necessary for the body. From this understanding of the immune regulation of MS, we can expect the development of therapeutic strategies that target only pathogenic immune cells.

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“…As an immunosuppressive molecule, IL-10 can restrict immune responses against pathogens and microbial communities, which is a key mechanism underlying its anti-inflammatory properties. Evidence suggests that IL-10 is expressed not only in bone marrow and lymphoid lineage cells but also in tumor-associated macrophages [5], epithelial cells [6], and innate immune cells of the central nervous system [7]. This broad anti-inflammatory profile has significant effects in preventing autoimmune diseases [8], balancing neuroimmune responses [7], and cancer therapy [9].…”

Section: Introductionmentioning

confidence: 99%

“…Evidence suggests that IL-10 is expressed not only in bone marrow and lymphoid lineage cells but also in tumor-associated macrophages [5], epithelial cells [6], and innate immune cells of the central nervous system [7]. This broad anti-inflammatory profile has significant effects in preventing autoimmune diseases [8], balancing neuroimmune responses [7], and cancer therapy [9].…”

Section: Introductionmentioning

confidence: 99%

A Stacking Machine Learning Method for IL-10-Induced Peptide Sequence Recognition Based on Unified Deep Representation Learning

Li,

Jiang,

Pei

et al. 2023

Applied Sciences

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Interleukin-10 (IL-10) has anti-inflammatory properties and is a crucial cytokine in regulating immunity. The identification of IL-10 through wet laboratory experiments is costly and time-intensive. Therefore, a new IL-10-induced peptide recognition method, IL10-Stack, was introduced in this research, which was based on unified deep representation learning and a stacking algorithm. Two approaches were employed to extract features from peptide sequences: Amino Acid Index (AAindex) and sequence-based unified representation (UniRep). After feature fusion and optimized feature selection, we selected a 1900-dimensional UniRep feature vector and constructed the IL10-Stack model using stacking. IL10-Stack exhibited excellent performance in IL-10-induced peptide recognition (accuracy (ACC) = 0.910, Matthews correlation coefficient (MCC) = 0.820). Relative to the existing methods, IL-10Pred and ILeukin10Pred, the approach increased in ACC by 12.1% and 2.4%, respectively. The IL10-Stack method can identify IL-10-induced peptides, which aids in the development of immunosuppressive drugs.

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IL-10-providing B cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity

Cited by 7 publications

References 42 publications

Systems Analysis of Immune Changes after B-cell Depletion in Autoimmune Multiple Sclerosis

Systems Analysis of Immune Changes after B-cell Depletion in Autoimmune Multiple Sclerosis

Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells

A Stacking Machine Learning Method for IL-10-Induced Peptide Sequence Recognition Based on Unified Deep Representation Learning

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