AUTHOR=Nagy Noémi Anna , Lozano Vigario Fernando , Sparrius Rinske , van Capel Toni M. M. , van Ree Ronald , Tas Sander W. , de Vries I. Jolanda M. , Geijtenbeek Teunis B. H. , Slütter Bram , de Jong Esther C. ,  for the DC4Balance consortium 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1137538

DOI=10.3389/fimmu.2023.1137538

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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 <italic>in vivo</italic> with nanoparticles incorporating tolerogenic adjuvants and auto-antigens or allergens.</p></sec><sec><title>Methods</title><p>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. </p></sec><sec><title>Results</title><p>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. </p></sec><sec><title>Discussion</title><p>These results suggest that nanoparticulate VD3 is a tolerogenic tool for DC-mediated induction of regulatory T cell responses.</p></sec>