Targeting macrophages with phosphatidylserine-rich liposomes as a potential antigen-specific immunotherapy for type 1 diabetes
García Loza, Iván (Institut de Recerca Sant Pau)
Perna-Barrull, David (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Aguilera, Eva (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Almenara-Fuentes, Lidia (Ahead Therapeutics SL)
Gómez Muñoz, Laia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Greco, Daniela (Ahead Therapeutics SL)
Vila, María (Ahead Therapeutics SL)
Salvado, Miriam (Ahead Therapeutics SL)
Mancera Arteu, Montserrat (Ahead Therapeutics SL)
Olszowy, Michael W. (Sartorius Stedim North America. Inc.)
Petriz, Jordi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Dalmases, Martí (Ahead Therapeutics SL)
Rodriguez-Vidal, Sílvia (Ahead Therapeutics SL)
Barneda Zahonero, Bruna (Ahead Therapeutics SL)
Vives Pi, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Type 1 diabetes (T1D) results from a breakdown in immunological tolerance, with pivotal involvement of antigen-presenting cells. In this context, antigen-specific immunotherapies have been developed to arrest autoimmunity, such as phosphatidylserine (PS)-liposomes. However, the role of certain antigen-presenting cells in immunotherapy, particularly human macrophages (Mφ) in T1D remains elusive. The aim of this study was to determine the role of Mφ in antigen-specific immune tolerance and T1D. To that end, we evaluated Mφ ability to capture apoptotic-body mimicking PS-liposomes in mice and conducted a phenotypic and functional characterisation of four human monocyte-derived Mφ (MoMφ) subpopulations (M0, M1, M2a and M2c) after PS-liposomes uptake. Our findings in mice identified Mφ as the most phagocytic cell subset in the spleen and liver. In humans, while phagocytosis rates were comparable between T1D and control individuals, PS-liposome capture dynamics differed among Mφ subtypes, favouring inflammatory (M1) and deactivated (M2c) Mφ. Notably, high nanoparticle concentrations did not affect macrophage viability. PS-liposome uptake by Mφ induced alterations in membrane molecule expression related to immunoregulation, reduced secretion of IL-6 and IL-12, and diminished autologous T-cell proliferation in the context of autoantigen stimulation. These results underscore the tolerogenic effects of PS-liposomes and emphasize their potential to target human Mφ, providing valuable insights into the mechanism of action of this preclinical immunotherapy.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Journal of autoimmunity, Vol. 145 (may 2024) , p. 103196, ISSN 1095-9157

DOI: 10.1016/j.jaut.2024.103196
PMID: 38458075

14 p, 8.5 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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