Glucocorticoid signaling mediates CD8+ T cell memory differentiation

Abstract

We provide evidence on the TRM potentiation by glucocorticoids in stimulated CD8+ T cells. Signaling via glucocorticoid receptor reciprocally regulated short-lived effector cells and memory precursor effector cells. Influenza A virus infected mice treated transiently with dexamethasone preferentially generated multipotent TRM cells that efficiently responded to the subsequent infection. Compromised memory following abrogation of glucocorticoid signaling further confirmed their role in memory potentiation. Transcriptomic and biochemical analysis of dexamethasone treated cells revealed a metabolic switch to oxidative phosphorylation via an engagement of AMPK signaling due to reduced glucose uptake. These cells exhibited an accumulation of phosphorylated STAT3 and STAT5 to drive memory differentiation. Therefore, glucocorticoids mediate tissue homing memory T cell differentiation. One-Sentence SummaryGlucocorticoid signaling in responding CD8+ T cells promotes memory differentiation