Stable inhibitory activity of regulatory T cells requires the transcription factor Helios
Hye-Jung Kim, R Anthony Barnitz, Taras Kreslavsky, Flavian D Brown, Howell Moffett, Madeleine E Lemieux, Yasemin Kaygusuz, Torsten Meissner, Tobias A W Holderried, Susan Chan, Philippe Kastner, W Nicholas Haining, Harvey Cantor, Hye-Jung Kim, R Anthony Barnitz, Taras Kreslavsky, Flavian D Brown, Howell Moffett, Madeleine E Lemieux, Yasemin Kaygusuz, Torsten Meissner, Tobias A W Holderried, Susan Chan, Philippe Kastner, W Nicholas Haining, Harvey Cantor
Abstract
The maintenance of immune homeostasis requires regulatory T cells (T(regs)). Given their intrinsic self-reactivity, T(regs) 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 T(regs) results in defective regulatory activity and autoimmunity in mice. Helios-deficient T(regs) 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 T(regs) 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 T(regs) in the face of inflammatory responses provides a genetic explanation for a core property of T(regs).
Copyright © 2015, American Association for the Advancement of Science.
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Source: PubMed