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


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

SUBMITTER: Friesen LR 

PROVIDER: S-EPMC7725911 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Friesen L R LR   Gu B B   Kim C H CH  

Mucosal immunology 20200609 1


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 togeth  ...[more]

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