A subset of Foxp3+ regulatory T (Treg) 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, Treg cells are phenotypically plastic. They can secrete proinflammatory cytokines and show T helper cell activity. Although some of these Treg 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+ Treg cells that in an inflammatory environment downregulate Eos, a co-repressor required for Foxp3-mediated Treg cell suppressive activity. These Eos-labile Treg 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 Treg cells impaired their reprogramming and T helper cell activity in vivo. In tumor-bearing mice, downregulation of Eos was impaired and Treg cell suppressive activity was maintained by indolemaine 2,3-dioxygenase (IDO). Inhibition of IDO promoted Treg cell reprogramming and antitumor immune responses.
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Da Silva, K. Reprogramming regulatory T cells. Nat Med 19, 826 (2013). https://doi.org/10.1038/nm.3274
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DOI: https://doi.org/10.1038/nm.3274