Liposomes loaded with vitamin D3 induce regulatory circuits in human dendritic cells.

Noémi Anna Nagy, Fernando Lozano Vigario, Rinske Sparrius, Toni M M van Capel, Ronald van Ree, Sander W Tas, I Jolanda M de Vries, Teunis B H Geijtenbeek, Bram Slütter, Esther C de Jong

Journal: Frontiers in immunology 2023;14():1137538

PMID: 37359530

Abstract

INTRODUCTION

Nanomedicine provides a promising platform for manipulating dendritic cells (DCs) and the ensuing adaptive immune response. For the induction of regulatory responses, DCs can be targeted with nanoparticles incorporating tolerogenic adjuvants and auto-antigens or allergens.

METHODS

Here, we investigated the tolerogenic effect of different liposome formulations loaded with vitamin D3 (VD3). We extensively phenotyped monocyte-derived DCs (moDCs) and skin DCs and assessed DC-induced regulatory CD4+ T cells in coculture.

RESULTS

Liposomal VD3 primed-moDCs induced the development of regulatory CD4+ T cells (Tregs) that inhibited bystander memory T cell proliferation. Induced Tregs were of the FoxP3+ CD127low phenotype, also expressing TIGIT. Additionally, liposome-VD3 primed moDCs inhibited the development of T helper 1 (Th1) and T helper 17 (Th17) cells. Skin injection of VD3 liposomes selectively stimulated the migration of CD14+ skin DCs.

DISCUSSION

These results suggest that nanoparticulate VD3 is a tolerogenic tool for DC-mediated induction of regulatory T cell responses.

Copyright © 2023 Nagy, Lozano Vigario, Sparrius, van Capel, van Ree, Tas, de Vries, Geijtenbeek, Slütter, de Jong and for the DC4Balance consortium.

Address: Amsterdam Universitair Medische Centra (UMC), Department of Experimental Immunology, Amsterdam Institute for Infection & Immunity, University of Amsterdam, Amsterdam, Netherlands.; Division of BioTherapeutics, Leiden Academic Center for Drug Research, Leiden, Netherlands.; Amsterdam Universitair Medische Centra (UMC), Department of Otorhinolaryngology, University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Universitair Medische Centra (UMC), Department of Rheumatology and Clinical Immunology, University of Amsterdam, Amsterdam, Netherlands.; Department of Tumor Immunology, Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
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