Regulatory T cells(Tregs)promote immune homeostasis by maintaining self-tolerance and regulating inflammatory *** certain inflammatory conditions,Tregs can lose their lineage stability and *** studies have reported th...
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Regulatory T cells(Tregs)promote immune homeostasis by maintaining self-tolerance and regulating inflammatory *** certain inflammatory conditions,Tregs can lose their lineage stability and *** studies have reported that ex vivo exposure to retinoic acid(ra)enhances Treg function and ***,it is unknown how ra receptor signaling in Tregs influences these processes in ***,we employed mouse models in which ra signaling is silenced by the expression of the dominant negative receptor(DN)raRαin all T *** the fact that DNraRαconventional T cells are hypofunctional,Tregs had increased CD25 expression,STAT5 pathway activation,mTORC1 signaling and supersuppressor ***,DNraRαTregs had increased inhibitory molecule expression,amino acid transporter expression,and metabolic fitness and decreased antiapoptotic *** function was observed when wild-type mice were treated with a pharmacologic pan-raR ***,Treg-specific expression of DNraRαresulted in distinct phenotypes,such that a single allele of DNraRαin Tregs heightened their suppressive function,and biallelic expression led to loss of suppression and *** loss of Treg function was not cell intrinsic,as Tregs that developed in a noninflammatory milieu in chimeric mice reconstituted with DNraRαand wild-type bone marrow maintained the enhanced suppressive *** mapping suggested that maintaining Treg stability in an inflammatory milieu requires ra *** findings indicate that ra signaling acts as a rheostat to balance Treg function in inflammatory and noninflammatory conditions in a dose-dependent manner.
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