CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

CD9 was recently identified as a marker of murine IL-10-competent regulatory B cells. Functional impairments or defects in CD9+ IL-10-secreting regulatory B cells are associated with enhanced asthma-like inflammation and airway hyperresponsiveness. In mouse models, all asthma-related features can be abrogated by CD9+ B cell adoptive transfer. We aimed herein to decipher the profiles, features, and molecular mechanisms of the regulatory properties of CD9+ B cells in human and mouse. The profile of CD9+ B cells was analyzed using blood from severe asthmatic patients and normal and asthmatic mice by flow cytometry. The regulatory effects of mouse CD9+ B cells on effector T cell death, cell cycle arrest, apoptosis, and mitochondrial depolarization were determined using yellow dye, propidium iodide, Annexin V, and JC-1 staining. MAPK phosphorylation was analyzed by western blotting. Patients with severe asthma and asthmatic mice both harbored less CD19+CD9+ B cells, although these cells displayed no defect in their capacity to induce T cell apoptosis. Molecular mechanisms of regulation of CD9+ B cells characterized in mouse showed that they induced effector T cell cycle arrest in sub G0/G1, leading to apoptosis in an IL-10-dependent manner. This process occurred through MAPK phosphorylation and activation of both the intrinsic and extrinsic pathways. This study characterizes the molecular mechanisms underlying the regulation of CD9+ B cells to induce effector T cell apoptosis in mice and humans via IL-10 secretion. Defects in CD9+ B cells in blood from patients with severe asthma reveal new insights into the lack of regulation of inflammation in these patients

Solid dosing in High-Throughput Experimentation: generalization of mass enhancer technologies for submilligram scale

International audienceThe emergence of High-Throughput Experimentation (HTE) as a powerful tool for reaction discovery and optimization is changing the way organic chemists are designing their experiments. It is a fantastic way to largely investigate a reaction, in a minimum of time and reagent consumption. However, HTE needs to be accessible to a wide audience for a full implementation in academic and industrial sectors. In that context, developing accessible solid dosing methodologies for submilligram dispensing is necessary. This paper aims at proposing robust mass enhancers solutions for nanomole scale dosing applicable to HTE campaigns

CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

International audienceCD9 was recently identified as a marker of murine IL-10-competent regulatory B cells. Functional impairments or defects in CD9 + IL-10-secreting regulatory B cells are associated with enhanced asthma-like inflammation and airway hyperresponsiveness. In mouse models, all asthma-related features can be abrogated by CD9 + B cell adoptive transfer. We aimed herein to decipher the profiles, features, and molecular mechanisms of the regulatory properties of CD9 + B cells in human and mouse. The profile of CD9 + B cells was analyzed using blood from severe asthmatic patients and normal and asthmatic mice by flow cytometry. The regulatory effects of mouse CD9 + B cells on effector T cell death, cell cycle arrest, apoptosis, and mitochondrial depolarization were determined using yellow dye, propidium iodide, Annexin V, and JC-1 staining. MAPK phosphorylation was analyzed by western blotting. Patients with severe asthma and asthmatic mice both harbored less CD19 + CD9 + B cells, although these cells displayed no defect in their capacity to induce T cell apoptosis. Molecular mechanisms of regulation of CD9 + B cells characterized in mouse showed that they induced effector T cell cycle arrest in sub G0/G1, leading to apoptosis in an IL-10-dependent manner. This process occurred through MAPK phosphorylation and activation of both the intrinsic and extrinsic pathways. This study characterizes the molecular mechanisms underlying the regulation of CD9 + B cells to induce effector T cell apoptosis in mice and humans via IL-10 secretion. Defects in CD9 + B cells in blood from patients with severe asthma reveal new insights into the lack of regulation of inflammation in these patients

High circulating CD4+CD25[hi]FOXP3+ T cell subpopulation early after lung transplantation is associated with development of BOS

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Increased degradation of ATP is driven by memory~regulatory T cells in kidney transplantation tolerance

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The β1-Adrenergic Receptor Contributes to Sepsis-Induced Immunosuppression Through Modulation of Regulatory T-Cell Inhibitory Function*

International audienceObjectives: Although cardiovascular benefits of β 1 -adrenergic receptor blockade have been described in sepsis, little is known about its impact on the adaptive immune response, specifically CD4 T cells. Herein, we study the effects of β 1 -adrenergic receptor modulation on CD4 T-cell function in a murine model of sepsis.Design: Experimental study.Setting: University laboratory.Subjects: C57BL/6 mice.Interventions: High-grade sepsis was induced by cecal ligation and puncture in wild-type mice (β 1+/+ ) with or without esmolol (a selective β 1 -adrenergic receptor blocker) or in β 1 -adrenergic receptor knockout mice (β 1-/- ). At 18 hours after surgery, echocardiography was performed with blood and spleen collected to analyze lymphocyte function.Measurements and main results: At 18 hours, β 1+/+ cecal ligation and puncture mice exhibited characteristics of high-grade sepsis and three surrogate markers of immunosuppression, namely decreased splenic CD4 T cells, reduced CD4 T-cell proliferation, and increased regulatory T lymphocyte cell proportions. Pharmacologic and genetic β 1 -adrenergic receptor blockade reversed the impact of sepsis on CD4 T and regulatory T lymphocyte proportions and maintained CD4 T-cell proliferative capacity. β 1 -adrenergic receptor blocked cecal ligation and puncture mice also exhibited a global decrease in both pro- and anti-inflammatory mediators and improved in vivo cardiovascular efficiency with maintained cardiac power index despite the expected decrease in heart rate.Conclusions: β 1 -adrenergic receptor activation enhances regulatory T lymphocyte inhibitory function and thus contributes to sepsis-induced immunosuppression. This can be attenuated by β 1 -adrenergic receptor blockade, suggesting a potential immunoregulatory role for this therapy in the management of sepsis

La loyauté : de la règle morale au principe juridique

Cherbonnier William, Crochet Lauryanne, Durand Eugénie, Favzlavaki Yannick, Figarol Valentine, Foix Jean Christophe, Gabillard Leo, Keh Luc, Le Gorgne Elodie, Morvan Jeremy, Sinaud Jean-Charles, Schultz Béverley, Tardif-Canneva Sabine. La loyauté : de la règle morale au principe juridique. In: Revue juridique de l'Ouest, 2012-3. pp. 327-342

Blood CD9+ B cell, a biomarker of bronchiolitis obliterans syndrome after lung transplantation

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Influence of the Immune Microenvironment Provided by Implanted Biomaterials on the Biological Properties of Masquelet-Induced Membranes in Rats: Metakaolin as an Alternative Spacer

International audienceMacrophages play a key role in the inflammatory phase of wound repair and foreign body reactions-two important processes in the Masquelet-induced membrane technique for extremity reconstruction. The macrophage response depends largely on the nature of the biomaterials implanted. However, little is known about the influence of the macrophage microenvironment on the osteogenic properties of the induced membrane or subsequent bone regeneration. We used metakaolin, an immunogenic material, as an alternative spacer to standard polymethylmethacrylate (PMMA) in a Masquelet model in rats. Four weeks after implantation, the PMMA-and metakaolin-induced membranes were harvested, and their osteogenic properties and macrophage microenvironments were investigated by histology, immunohistochemistry, mass spectroscopy and gene expression analysis. The metakaolin spacer induced membranes with higher levels of two potent pro-osteogenic factors, transforming growth factor-β (TGF-β) and bone morphogenic protein-2 (BMP-2). These alternative membranes thus had greater osteogenic activity, which was accompanied by a significant expansion of the total macrophage population, including both the M1-like and M2-like subtypes. Microcomputed tomographic analysis showed that metakaolin-induced membranes supported bone regeneration more effectively than PMMA-induced membranes through better callus properties (+58%), although this difference was not significant. This study provides the first evidence of the influence of the immune microenvironment on the osteogenic properties of the induced membranes