Stable inhibitory activity of regulatory T cells requires the transcription factor Helios

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Science  16 Oct 2015:
Vol. 350, Issue 6258, pp. 334-339
DOI: 10.1126/science.aad0616

How T cells maintain their identity

Although best known for their pathogen-fighting prowess, T lymphocytes also ensure that the immune response does not run amok. A subset of T cells called regulatory T cells (Tregs) performs this function by, for example, making sure T cells only attack pathogens and not self. T cells can exhibit plasticity in their functions in the face of an inflammatory stimulus. Kim et al. sought to identify the molecules that ensure the stable maintenance of Tregs. Using genetically modified mice, they found that both CD4+ and CD8+ Tregs require the transcription factor Helios to stably maintain their identity.

Science, this issue p. 334


The maintenance of immune homeostasis requires regulatory T cells (Tregs). Given their intrinsic self-reactivity, Tregs must stably maintain a suppressive phenotype to avoid autoimmunity. We report that impaired expression of the transcription factor (TF) Helios by FoxP3+ CD4 and Qa-1–restricted CD8 Tregs results in defective regulatory activity and autoimmunity in mice. Helios-deficient Tregs develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. CD8 Tregs also require Helios-dependent STAT5 activation for survival and to prevent terminal T cell differentiation. The definition of Helios as a key transcription factor that stabilizes Tregs in the face of inflammatory responses provides a genetic explanation for a core property of Tregs.

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