Journal
NATURE IMMUNOLOGY
Volume 15, Issue 10, Pages 947-U192Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2960
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Funding
- US National Institutes of Health Intramural Research Programs of the National Cancer Institute, Center for Cancer Research
- National Institute of Allergy and Infectious Diseases
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
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The transcription factor ThPOK promotes CD4(+) T cell differentiation in the thymus. Here, using a mouse strain that allows post-thymic gene deletion, we show that ThPOK maintains CD4(+) T lineage integrity and couples effector differentiation to environmental cues after antigenic stimulation. ThPOK preserved the integrity and amplitude of effector responses and was required for proper differentiation of types 1 and 2 helper T cells in vivo by restraining the expression and function of Runx3, a nuclear factor crucial for cytotoxic T cell differentiation. The transcription factor LRF acts redundantly with ThPOK to prevent the transdifferentiation of mature CD4(+) T cells into CD8(+) T cells. As such, the ThPOK-LRF transcriptional module was essential for CD4(+) T cell integrity and responses.
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