Retinoic acid-loaded liposomes induce human mucosal CD103 + dendritic cells that inhibit Th17 cells and drive regulatory T-cell development in vitro.
Noémi Anna NagyFlorianne M J HafkampRinske SparriusRico BasFernando Lozano VigarioToni M M van CapelRonald van ReeTeunis B H GeijtenbeekBram SlütterSander W TasEsther C de JongPublished in: European journal of immunology (2024)
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.
Keyphrases
- dendritic cells
- regulatory t cells
- drug delivery
- rheumatoid arthritis
- immune response
- disease activity
- cell proliferation
- ankylosing spondylitis
- endothelial cells
- drug release
- poor prognosis
- stem cells
- cell therapy
- single cell
- cancer therapy
- induced apoptosis
- ulcerative colitis
- high glucose
- prognostic factors
- induced pluripotent stem cells
- cell cycle
- celiac disease
- mesenchymal stem cells
- pluripotent stem cells
- single molecule
- atomic force microscopy