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Retinoic acid‐loaded liposomes induce human mucosal CD103+ dendritic cells that inhibit Th17 cells and drive regulatory T‐cell development in vitro

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 celia...

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Published in:European journal of immunology 2024-05, Vol.54 (5), p.e2350839-n/a
Main Authors: Nagy, Noémi Anna, Hafkamp, Florianne M. J., Sparrius, Rinske, Bas, Rico, Lozano Vigario, Fernando, Capel, Toni M. M., Ree, Ronald, Geijtenbeek, Teunis B. H., Slütter, Bram, Tas, Sander W., Jong, Esther C.
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cited_by cdi_FETCH-LOGICAL-c4034-9271cee64f7c0a72045189d1772d65f6afc4cd6912a3ee59185c77d11cf383fd3
cites cdi_FETCH-LOGICAL-c4034-9271cee64f7c0a72045189d1772d65f6afc4cd6912a3ee59185c77d11cf383fd3
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container_title European journal of immunology
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creator Nagy, Noémi Anna
Hafkamp, Florianne M. J.
Sparrius, Rinske
Bas, Rico
Lozano Vigario, Fernando
Capel, Toni M. M.
Ree, Ronald
Geijtenbeek, Teunis B. H.
Slütter, Bram
Tas, Sander W.
Jong, Esther C.
description 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. In vitro, RA liposomes drive human monocytes to differentiate into CD103+ mucosal‐like DCs that inhibit Th17 cell development and induce FoxP3+ and IL‐10‐producing T cells. RA liposomes prime human moDCs to shift T‐cell polarization and induce regulatory T cells expressing FoxP3 and IL‐10 in vitro.
doi_str_mv 10.1002/eji.202350839
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J. ; Sparrius, Rinske ; Bas, Rico ; Lozano Vigario, Fernando ; Capel, Toni M. M. ; Ree, Ronald ; Geijtenbeek, Teunis B. H. ; Slütter, Bram ; Tas, Sander W. ; Jong, Esther C.</creator><creatorcontrib>Nagy, Noémi Anna ; Hafkamp, Florianne M. J. ; Sparrius, Rinske ; Bas, Rico ; Lozano Vigario, Fernando ; Capel, Toni M. M. ; Ree, Ronald ; Geijtenbeek, Teunis B. H. ; Slütter, Bram ; Tas, Sander W. ; Jong, Esther C.</creatorcontrib><description>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. 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ispartof European journal of immunology, 2024-05, Vol.54 (5), p.e2350839-n/a
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subjects Adjuvants
Aldehyde Dehydrogenase 1 Family
Antigens
Antigens, CD - immunology
Antigens, CD - metabolism
CD103 antigen
Celiac disease
Celiac Disease - immunology
Cell Differentiation - drug effects
Cell Differentiation - immunology
Cell proliferation
Cells, Cultured
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic cells(s)
Forkhead Transcription Factors - metabolism
Foxp3 protein
Helper cells
Humans
Immune regulation
Immune Tolerance - drug effects
Immunological tolerance
Immunoregulation
Immunotherapy
Inflammatory bowel disease
Inflammatory bowel diseases
Inflammatory Bowel Diseases - immunology
Integrin alpha Chains - metabolism
Interleukin-10 - immunology
Interleukin-10 - metabolism
Leukocytes (neutrophilic)
Liposomes
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Lymphocytes T
Monocytes
Mucosa
Mucosal immunity
Nanoparticles
Phenotypes
Regulatory T cell(s)
Retinal Dehydrogenase - metabolism
Retinoic acid
T-Lymphocytes, Regulatory - drug effects
T-Lymphocytes, Regulatory - immunology
Th17 Cells - immunology
Tretinoin - pharmacology
Vitamin A
title Retinoic acid‐loaded liposomes induce human mucosal CD103+ dendritic cells that inhibit Th17 cells and drive regulatory T‐cell development in vitro
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