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

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2015-10, Vol.350 (6258), p.334-339
Main Authors: Kim, Hye-Jung, Barnitz, R. Anthony, Kreslavsky, Taras, Brown, Flavian D., Moffett, Howell, Lemieux, Madeleine E., Kaygusuz, Yasemin, Meissner, Torsten, Holderried, Tobias A. W., Chan, Susan, Kastner, Philippe, Haining, W. Nicholas, Cantor, Harvey
Format: Article
Language:English
Subjects:
Activation
Animals
Autoimmunity - genetics
Autoimmunity - immunology
CD8-Positive T-Lymphocytes - immunology
DNA-Binding Proteins - biosynthesis
DNA-Binding Proteins - genetics
Forkhead Transcription Factors - immunology
Gene Expression
Genetics
Government regulations
Immune system
Individualized Instruction
Inflammation
Kidney - immunology
Liver - immunology
Lymphocyte Activation
Lymphocytes
Maintenance
Mice
Mice, Inbred C57BL
Mice, Transgenic
Pancreas - immunology
Pathogens
Protein expression
STAT5 Transcription Factor - metabolism
T-Lymphocytes, Regulatory - immunology
Terminals
Transcription Factors - biosynthesis
Transcription Factors - genetics
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aad0616