Retinoic acid signalling is required for the pathogenicity of effector CD4+ T cells during the development of intestinal inflammation

Aymeric Marie Christian Rivollier, Lieneke Pool, Ulrika Frising, Kerstin Wendland, William Winston Agace

    Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

    Abstract

    The vitamin A metabolite retinoic acid (RA) seems to be a double-edge sword in CD4+ T cell biology, sustaining the development of foxp3+ Treg cells, but also being essential for the stability of the Th1 lineage. Here we explored the role of RA signalling in CD4+ T cells during the development of intestinal inflammation in the T cell transfer colitis model. RA signalling-deficient CD4+ T cells are less potent at inducing intestinal inflammation compared to their RA signalling-proficient counterparts and exhibit a differentiation skewing towards more IL-17+ and foxp3+ cells, while their capacity to differentiate into Th1 cells is compromised. In vitro studies confirm the inefficacy of RA signalling-deficient T cells to generate bona fide Th1 cells and demonstrate their aberrant increased RORγt expression, while their Th17 differentiation remains unaffected. Surprisingly, RA signalling-deficient and –proficient Tregs are equally competent to inhibit colitis development. Together our results indicate that RA, through its receptor RARα, negatively regulates the early expansion of CD4+ T cells during colitis and is necessary for the generation of colitogenic Th1/Th17 cells, while it is dispensable for the protective function of Treg cells. We are currently deciphering the mechanisms of these effects of RA on CD4+ T cells.
    Original languageEnglish
    Publication date2016
    Number of pages1
    Publication statusPublished - 2016
    Event10th European Mucosal Immunology Group meeting - Copenhagen, Denmark
    Duration: 19 Oct 201621 Oct 2016
    Conference number: 10

    Conference

    Conference10th European Mucosal Immunology Group meeting
    Number10
    CountryDenmark
    CityCopenhagen
    Period19/10/201621/10/2016

    Cite this

    Rivollier, A. M. C., Pool, L., Frising, U., Wendland, K., & Agace, W. W. (2016). Retinoic acid signalling is required for the pathogenicity of effector CD4+ T cells during the development of intestinal inflammation. Abstract from 10th European Mucosal Immunology Group meeting, Copenhagen, Denmark.