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Repeated immunization with ATRA-containing liposomal adjuvant transdifferentiates Th17 cells to a Tr1-like phenotype.

Authors :
Wørzner K
Zimmermann J
Buhl R
Desoi A
Christensen D
Dietrich J
Nguyen NDNT
Lindenstrøm T
Woodworth JS
Alhakeem RS
Yu S
Ødum N
Mortensen R
Ashouri JF
Pedersen GK
Source :
Journal of autoimmunity [J Autoimmun] 2024 Apr; Vol. 144, pp. 103174. Date of Electronic Publication: 2024 Feb 19.
Publication Year :
2024

Abstract

In many autoimmune diseases, autoantigen-specific Th17 cells play a pivotal role in disease pathogenesis. Th17 cells can transdifferentiate into other T cell subsets in inflammatory conditions, however, there have been no attempts to target Th17 cell plasticity using vaccines. We investigated if autoantigen-specific Th17 cells could be specifically targeted using a therapeutic vaccine approach, where antigen was formulated in all-trans retinoic acid (ATRA)-containing liposomes, permitting co-delivery of antigen and ATRA to the same target cell. Whilst ATRA was previously found to broadly reduce Th17 responses, we found that antigen formulated in ATRA-containing cationic liposomes only inhibited Th17 cells in an antigen-specific manner and not when combined with an irrelevant antigen. Furthermore, this approach shifted existing Th17 cells away from IL-17A expression and transcriptomic analysis of sorted Th17 lineage cells from IL-17 fate reporter mice revealed a shift of antigen-specific Th17 cells to exTh17 cells, expressing functional markers associated with T cell regulation and tolerance. In the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, vaccination with myelin-specific (MOG) antigen in ATRA-containing liposomes reduced Th17 responses and alleviated disease. This highlights the potential of therapeutic vaccination for changing the phenotype of existing Th17 cells in the context of immune mediated diseases.<br /> (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Details

Language :
English
ISSN :
1095-9157
Volume :
144
Database :
MEDLINE
Journal :
Journal of autoimmunity
Publication Type :
Academic Journal
Accession number :
38377868
Full Text :
https://doi.org/10.1016/j.jaut.2024.103174