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

Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 1273201 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-4141 (Electronic) Linking ISSN: 00142980 NLM ISO Abbreviation: Eur J Immunol Subsets: MEDLINE

Publication: <2005->: Weinheim : Wiley-VCH
Original Publication: Weinheim, Verlag Chemie GmbH.

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*; 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

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.)

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Health Holland- SGF

Keywords: Dendritic cells(s); Immune regulation; Immunotherapy; Mucosal immunity; Regulatory T cell(s)

5688UTC01R (Tretinoin)
0 (Integrin alpha Chains)
0 (alpha E integrins)
0 (Antigens, CD)
0 (Liposomes)
EC 1.2.1.36 (Retinal Dehydrogenase)
EC 1.2.1 (Aldehyde Dehydrogenase 1 Family)
EC 1.2.1.36 (ALDH1A2 protein, human)
130068-27-8 (Interleukin-10)
0 (Forkhead Transcription Factors)
0 (FOXP3 protein, human)

Date Created: 20240302 Date Completed: 20240507 Latest Revision: 20240507

20240508

10.1002/eji.202350839

38430190