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- Title
Retinoic acid‐loaded liposomes induce human mucosal CD103<sup>+</sup> dendritic cells that inhibit Th17 cells and drive regulatory T‐cell development in vitro.
- Authors
Nagy, Noémi Anna; Hafkamp, Florianne M. J.; Sparrius, Rinske; Bas, Rico; Lozano Vigario, Fernando; van Capel, Toni M. M.; van Ree, Ronald; Geijtenbeek, Teunis B. H.; Slütter, Bram; Tas, Sander W.; de Jong, Esther C.
- 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.
- Subjects
T helper cells; TRETINOIN; REGULATORY T cells; DENDRITIC cells; LIPOSOMES; T cells
- Publication
European Journal of Immunology, 2024, Vol 54, Issue 5, p1
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.202350839