Reprogramming regulatory T cells

A subset of Foxp3⁺ regulatory T (T_reg) cells is now shown to be capable of acquiring T helper cell activity by downregulating expression of the transcription factor Eos (Immunity 38, 998–1012).

In an inflammatory environment, T_reg cells are phenotypically plastic. They can secrete proinflammatory cytokines and show T helper cell activity. Although some of these T_reg cells downregulate the expression of Foxp3, a transcription factor required for suppressive activity, some can maintain Foxp3 expression.

Madhav D. Sharma et al. identified a subset of Foxp3⁺ T_reg cells that in an inflammatory environment downregulate Eos, a co-repressor required for Foxp3-mediated T_reg cell suppressive activity. These Eos-labile T_reg cells upregulated interleukin-2 (IL-2), IL-17 and CD40 ligand and showed T helper cell activity while remaining Foxp3⁺. IL-6 promoted the downregulation of Eos, whereas overexpression of Eos in T_reg cells impaired their reprogramming and T helper cell activity in vivo. In tumor-bearing mice, downregulation of Eos was impaired and T_reg cell suppressive activity was maintained by indolemaine 2,3-dioxygenase (IDO). Inhibition of IDO promoted T_reg cell reprogramming and antitumor immune responses.