A ligand-independent fast function of RARα promotes exit from metabolic quiescence upon T cell activation and controls T cell differentiation.

Mucosal Immunology
Leon FriesenChang H Kim

Abstract

Vitamin A metabolites play important roles in T cell activation and differentiation. A conventional model of RARα function relies upon retinoic acid (RA)-liganded RARα binding to specific DNA motifs to regulate gene expression in the nucleus. However, this genomic function fails to explain many of the biological responses of the RA-RARα axis on T cells. We generated a mouse line where RARα is over-expressed in T cells to probe RARα function with unprecedented sensitivity. Using this model together with mice specifically lacking RARα in T cells, we found that RARα is required for prompt exit from metabolic quiescence in resting T cells upon T cell activation. The positive effect of RARα on metabolism is mediated through PI3K and subsequent activation of the Akt and mTOR signaling pathway. This largely non-genomic function of RARα is surprisingly ligand-independent and controls the differentiation of effector and regulatory T cell subsets.

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Citations

Mar 3, 2021·Blood·Marie-Claude GeoffroyHugues de Thé
May 26, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amélie CattinPetronela Ancuta
Sep 12, 2021·Nature Reviews. Clinical Oncology·Renumathy DhanasekaranDean W Felsher

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Methods Mentioned

BETA
proximity ligation assay
confocal microscopy
flow cytometry
transgenic
genotyping
PCR

Software Mentioned

ImageJ
GraphPad Prism

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