Phosphatidylserine Outer Layer Translocation Is Implicated in IL-10 Secretion by Human Regulatory B Cells

Audo, Rachel; Hua, C.; Hahne, Michael; Combe, Bernard; Morel, Jacques; Daïen, C.

doi:10.1371/journal.pone.0169755

Cited by 17 publications

(10 citation statements)

References 32 publications

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“…Subsequently, it was demonstrated that the mucin domain of TIM-1 was crucial for IL-10 induction by B cells following stimulation with PS-containing apoptotic cells, suggesting a physiologic pathway whereby dying cells promote tolerance to self-antigens and resolution of inflammation by activating IL-10 + TIM-1 + Bregs ( 503 – 505 ). This proposition is further sustained by observations in mice with a B cell-specific deletion of TIM-1 or mice lacking the mucin domain of TIM-1, which present a profound defect in IL-10 + Bregs and multi-organ tissue inflammation.…”

Section: Tim-1-expressing Bregs (Tim-1 + Bregs)mentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory B Cells

et al. 2021

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Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

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Section: Tim-1-expressing Bregs (Tim-1 + Bregs)mentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory B Cells

et al. 2021

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“…The start of the apoptotic pathway is characterised by the translocation of phosphatidylserine (PS) from the inner leaflet to the outer membrane and as a result, enables binding of annexin-V to PS [ 30 ]. The annexin-V-FITC positive and PI negative labelled cells were considered as early apoptotic cells and were represented in green on the flow cytometric scattergrams (Fig 5 a, b).…”

Section: Methodsmentioning

confidence: 99%

Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme

et al. 2021

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Glioblastoma multiforme (GBM) is an incurable aggressive brain cancer in which current treatment strategies have demonstrated limited survival benefit. In recent years, nitrogen-containing bisphosphonates (N-BPs) have demonstrated direct anticancer effects in a number of tumour types including GBM. In this study, a nano-formulation with the RALA peptide was used to complex the N-BP, alendronate (ALN) into nanoparticles (NPs) < 200 nm for optimal endocytic uptake. Fluorescently labelled AlexaFluor®647 Risedronate was used as a fluorescent analogue to visualise the intracellular delivery of N-BPs in both LN229 and T98G GBM cells. RALA NPs were effectively taken up by GBM where a dose-dependent response was evidenced with potentiation factors of 14.96 and 13.4 relative to ALN alone after 72 h in LN229 and T98G cells, respectively. Furthermore, RALA/ALN NPs at the IC50, significantly decreased colony formation, induced apoptosis and slowed spheroid growth in vitro. In addition, H-Ras membrane localisation was significantly reduced in the RALA/ALN groups compared to ALN or controls, indicative of prenylation inhibition. The RALA/ALN NPs were lyophilised to enhance stability without compromising the physiochemical properties necessary for functionality, highlighting the suitability of the NPs for scale-up and in vivo application. Collectively, these data show the significant potential of RALA/ALN NPs as novel therapeutics in the treatment of GBM.

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“…The start of the apoptotic pathway is characterised by the translocation of phosphatidylserine (PS) from the inner lea et to the outer membrane and as a result, enables binding of annexin-V to PS. 29 The annexin-V-FITC positive and PI negative labelled cells were considered as early apoptotic cells and were represented in green on the ow cytometric scattergrams (Fig. 5A-B).…”

Section: Rala/aln Nps Induce Apoptosis and Inhibit The Prenylation Ofmentioning

confidence: 99%

Exploiting the Anticancer Effects of a Nitrogen Bisphosphonate Nanomedicine for Glioblastoma Multiforme

Jena

Bennie

McErlean

et al. 2020

Preprint

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Glioblastoma multiforme (GBM) is an incurable aggressive brain cancer in which current treatment strategies have demonstrated limited survival benefit. In recent years, nitrogen-containing bisphosphonates (N-BPs) have demonstrated direct anticancer effects in a number of tumour types including GBM. In this study, a nano-formulation with the RALA peptide was used to complex the N-BP, alendronate (ALN) into nanoparticles (NPs) <200 nm for optimal endocytic uptake. Fluorescently labelled AlexaFluor®647 Risedronate was used as a fluorescent analogue to visualise the intracellular delivery of N-BPs in both LN229 and T98G GBM cells. RALA NPs were effectively taken up by GBM where a dose-dependent response was evidenced with potentiation factors of 14.96 and 13.4 relative to ALN alone after 72 h in LN229 and T98G cells, respectively. Furthermore, RALA/ALN NPs at the IC50, significantly decreased colony formation, induced apoptosis and slowed spheroid growth in vitro. In addition, H-Ras membrane localisation was significantly reduced in the RALA/ALN groups compared to ALN or controls, indicative of prenylation inhibition. The RALA/ALN NPs were lyophilised to enhance stability without compromising the physiochemical properties necessary for functionality, highlighting the suitability of the NPs for scale-up and in vivo application. Collectively, these data show the significant potential of RALA/ALN NPs as novel therapeutics in the treatment of GBM.

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Phosphatidylserine Outer Layer Translocation Is Implicated in IL-10 Secretion by Human Regulatory B Cells

Cited by 17 publications

References 32 publications

Immunosuppressive Mechanisms of Regulatory B Cells

Immunosuppressive Mechanisms of Regulatory B Cells

Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme

Exploiting the Anticancer Effects of a Nitrogen Bisphosphonate Nanomedicine for Glioblastoma Multiforme

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