Phosphatidylserine-Liposomes Promote Tolerogenic Features on Dendritic Cells in Human Type 1 Diabetes by Apoptotic Mimicry

Frontiers in Immunology
Silvia Rodríguez-FernándezMarta Vives-Pi

Abstract

Type 1 diabetes (T1D) is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow β-cell recovery has become vital. Relying on the inherent ability of apoptotic cells to induce immunological tolerance, we demonstrated that liposomes mimicking apoptotic β-cells arrested autoimmunity to β-cells and prevented experimental T1D through tolerogenic dendritic cell (DC) generation. These liposomes contained phosphatidylserine (PS)-the main signal of the apoptotic cell membrane-and β-cell autoantigens. To move toward a clinical application, PS-liposomes with optimum size and composition for phagocytosis were loaded with human insulin peptides and tested on DCs from patients with T1D and control age-related subjects. PS accelerated phagocytosis of liposomes with a dynamic typical of apoptotic cell clearance, preserving DCs viability. After PS-liposomes phagocytosis, the expression pattern of molecules involved in efferocytosis, antigen presentation, immunoregulation, and activation in DCs concurred with a tolerogenic functionality, both in patients and control subjects. Furthermore, DCs exposed to PS-...Continue Reading

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Citations

Dec 5, 2019·European Journal of Immunology·Bernhard KratzerWinfried F Pickl
Mar 25, 2020·Immunological Investigations·Fiona Y GlassmanSathy V Balu-Iyer
Apr 17, 2020·Frontiers in Immunology·José M CarballidoMichael Kammüller
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Aug 28, 2020·Frontiers in Bioengineering and Biotechnology·Ruichen ZhaoXin Zhang
Dec 5, 2019·Frontiers in Immunology·Andrea Kristina HorstLinda Diehl
Jan 24, 2021·Immunology and Cell Biology·Silvia Rodriguez-FernandezMarta Vives-Pi
Apr 3, 2021·Journal for Immunotherapy of Cancer·Dong Ho ShinJuan Fueyo
May 8, 2021·Frontiers in Immunology·Charles Yin, Bryan Heit
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Datasets Mentioned

BETA
GM-CSF
PRJEB22240

Methods Mentioned

BETA
density gradient centrifugation
flow cytometry
protein assay
dynamic light scattering
transmission electron microscopy
ELISA
Assay
RNA-seq
Fluorescence

Software Mentioned

GraphPad
FlowJo
Prism
CLCBio
limma Bioconductor
FASTQC
Ingenuity Pathway Analysis Software ( QIAGEN )
Protein Analysis Through Evolutionary Relationships Classifica...
R
CLCBio Genomics Workbench

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