Retinoic acid signalling is required for the efficient differentiation of CD4+ T cells into pathogenic effector cells during the development of intestinal inflammation

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

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    Abstract

    Epidemiological studies of vitamin A-deficient populations have illustrated the importance of the vitamin A metabolite retinoic acid (RA) in mucosal immune responses. However, RA seems to be a double-edge sword in CD4+ T cell biology. While it sustains the development of foxp3+ regulatory T cells, it was also very recently reported to be essential for the stability of the Th1 lineage and to prevent transition to a Th17 program.
    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. We found that RA signalling-deficient CD4+ T cells are less potent at inducing intestinal inflammation compared to their RA signalling-competent counterparts and exhibit a differentiation skewing towards more IFNγ- IL-17+, IL-17+IFNγ+ and foxp3+ cells, while their capacity to differentiate into IL-17-IFNγ+ 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 differentiation into Th17 remains unaffected. Surprisingly, RA signalling-deficient CD45RBlo regulatory T cells (Tregs) are however as efficient as their RA signalling-competent counterparts 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 date2015
    Number of pages1
    Publication statusPublished - 2015
    Event17th International Congress of Mucosal Immunology - Maritim Hotel, Berlin, Germany
    Duration: 14 Jul 201518 Jul 2015

    Conference

    Conference17th International Congress of Mucosal Immunology
    LocationMaritim Hotel
    CountryGermany
    CityBerlin
    Period14/07/201518/07/2015

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    Cite this

    Rivollier, A. M. C., Pool, L., Frising, U., Wendland, K., & Agace, W. W. (2015). Retinoic acid signalling is required for the efficient differentiation of CD4+ T cells into pathogenic effector cells during the development of intestinal inflammation. Abstract from 17th International Congress of Mucosal Immunology , Berlin, Germany.