Memory of Inflammation in Regulatory T Cells

Eukaryotic cells can “remember” transient encounters with a wide range of stimuli, inducing lasting states of altered responsiveness. Regulatory T (Treg) cells are a specialized lineage of suppressive CD4 T cells that act as critical negative regulators of inflammation in various biological contexts. Treg cells exposed to inflammatory conditions acquire strongly enhanced suppressive function. Using inducible genetic tracing, we analyzed the long-term stability of activation-induced transcriptional, epigenomic, and functional changes in Treg cells. We found that the inflammation-experienced Treg cell population reversed many activation-induced changes and lost its enhanced suppressive function over time. The “memory-less” potentiation of Treg suppressor function may help avoid a state of generalized immunosuppression that could otherwise result from repeated activation. [Display omitted] •Distinct features of resting, activated, and inflammation-experienced Treg cells•Inflammation-experienced Treg cells reverse many activation-induced changes•Resting Treg cells are transcriptionally similar to conventional memory CD4 T cells•Conventional memory CD4 T cells have limited potential for further differentiation Most inflammation-induced changes in Treg cell transcriptome, epigenome, and function are transient. A largely reversible activation state may enable potentiation of Treg cell function under inflammatory conditions, while avoiding long-lasting immunosuppression.