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This TCR affinity leads to the signalling of determined intensity during tTreg ontogenesis that orchestrates several epigenetic mechanisms involving Treg-specific superenchancers to establish a Treg-specific DNA demethylation profile and FOXP3 expression that ultimately ensures their functional stability in the periphery [18] (Fig

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10.1016/j.semarthrit.2025.152652 39 CoaccioliS.Sarzi-PuttiniP.ZisP.RinonapoliG.VarrassiG

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