1. Retinoic acid-loaded liposomes induce human mucosal CD103 + dendritic cells that inhibit Th17 cells and drive regulatory T-cell development in vitro.
- Author
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Nagy NA, Hafkamp FMJ, Sparrius R, Bas R, Lozano Vigario F, van Capel TMM, van Ree R, Geijtenbeek TBH, Slütter B, Tas SW, and de Jong EC
- Subjects
- Humans, Immune Tolerance drug effects, Cells, Cultured, Interleukin-10 metabolism, Interleukin-10 immunology, Forkhead Transcription Factors metabolism, Inflammatory Bowel Diseases immunology, Lymphocyte Activation drug effects, Lymphocyte Activation immunology, Celiac Disease immunology, Tretinoin pharmacology, Integrin alpha Chains metabolism, Th17 Cells immunology, Dendritic Cells immunology, Dendritic Cells drug effects, Antigens, CD immunology, Antigens, CD metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory drug effects, Liposomes, Cell Differentiation drug effects, Cell Differentiation immunology, Retinal Dehydrogenase metabolism, Aldehyde Dehydrogenase 1 Family
- Abstract
The active vitamin A metabolite, all-trans-retinoic acid (RA), primes precursor dendritic cells (DCs) into a mucosal phenotype with tolerogenic properties characterized by the expression of integrin CD103. CD103
+ DCs can counteract pathogenic Th1 and Th17 in inflammatory bowel disease (IBD) or celiac disease (CD). Tolerogenic manipulation of DCs using nanoparticles carrying tolerogenic adjuvants and disease-specific antigens is a valuable treatment strategy to induce antigen-specific mucosal tolerance in vivo. Here, we investigated the effects of RA-loaded liposomes on human DC phenotype and function, including DC-driven T-cell development, both during the generation of monocyte-derived DCs (moDCs) as well as by priming immature moDCs. RA liposomes drove CD103+ DC differentiation as well as ALDH1A2 expression in DCs. Neutrophil-dependent Th17 cell development was reduced by RA-liposome-differentiated and RA-liposome-primed DCs. Moreover, RA liposome treatment shifted T-cell development toward a Th2 cell profile. Importantly, RA liposomes induced the development of IL-10-producing and FoxP3+ regulatory T cells (Tregs) of various Treg subsets, including ICOS+ Tregs, that were potent inhibitors of bystander memory T-cell proliferation. Taken together, RA-loaded liposomes could be a novel treatment avenue for IBD or CD patients., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)- Published
- 2024
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