Pluto Bioinformatics

GSE96960: Alloantigen-specific regulatory T cells generated in presence of vitaminC display enhanced stability of Foxp3 expression and promote skin allograft acceptance

Bulk RNA sequencing

Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and selftolerance, and can be therapeutically used for prevention of unwanted immune responses such as allotransplant rejection. Tregs are characterized by the expression of the transcription factor Foxp3, and recent work suggested that epigenetic imprinting of Foxp3 and other Tregspecific epigenetic signatures genes is crucial for the stabilization of both Foxp3 expression and immunosuppressive properties within Tregs. Lately, VitaminC was reported to enhance the activity of enzymes of the teneleventranslocation family, thereby fostering the demethylation of Foxp3 and other Tregspecific epigenetic signatures genes in developing Tregs. Here, we invitro generated alloantigenspecific Foxp3+Tregs (alloiTregs) in presence of vitaminC, and those Tregs showed a pronounced demethylation of Foxp3 and other Tregspecific epigenetic signatures genes, accompanied with an enhanced stability of Foxp3 expression. However, RNAseq analysis revealed an only minor impact of VitaminC on the transcriptome of alloiTregs. Importantly, when being tested invivo in a highly immunogenic skin transplantation model vitaminCtreated alloiTregs showed a superior suppressive capacity as compared to alloiTregs generated in absence of vitaminC. Together, our results might pave the way for the establishment of novel protocols for the invitro generation of alloantigen specific Foxp3+Tregs for therapeutic usage in transplantation medicine. SOURCE: Michael BeckstetteExperimental Immunology Helmholtz Centre for Infection Research