BioProject

Th17 cells can transdifferentiate into other T cell subsets in the context of infections or inflammatory conditions. More...

Th17 cells can transdifferentiate into other T cell subsets in the context of infections or inflammatory conditions. In many autoimmune diseases, autoantigen-specific Th17 cells play a pivotal role in disease pathogenesis, however, there have been no attempts to target Th17 cell plasticity using vaccines. We aimed to change the phenotype of existing Th17 cells by a protein-in-adjuvant approach and found that antigen formulated in all-trans retinoic acid (ATRA)-containing cationic liposomes (CAF16) effectively inhibited existing Th17 responses. Strikingly, transcriptomic analysis of sorted Th17 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 addition, vaccination with myelin-specific (MOG) antigen in CAF16 reduced Th17 responses and alleviated disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. This highlights CAF16 as a novel delivery system for ATRA with potential for changing the phenotype of existing Th17 cells in the context of immune mediated diseases. Overall design: Cells from the spleen of IL-17A fate reporter mice immunized with either CAF01:H56 two times with two weeks in between (n = 10) or followed by four immunizations with CAF16:H56 were processed and stimulated with H56 (1 μg/ml) for 6 hours at 37 oC. Next, CD4+ T cells were isolated using the EasySep mouse CD4+ T cell isolation kit (STEMCELL Technologies Inc., Canada) according to the manufacturer’s recommendation. Live YFP+ cells were sorted using a BD FACSAria™ Cell Sorter (BD BioSciences). Cells were prepared for sequencing using the BD Rhapsody™ Immune Response Panel Mm (Cat.no: 633753, 397 genes, BD BioSciences) and the BD Rhapsody™ Scanner (BD BioSciences) according to the manufacture’s recommendations. Libraries were run on the NovaSeq 6000 with the NovaSeq 6000 SP reagent kit v1.5 (Illumina). Less...