Abstract
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.
Publication types
-
Research Support, N.I.H., Intramural
MeSH terms
-
Animals
-
CD4-Positive T-Lymphocytes / immunology*
-
CD4-Positive T-Lymphocytes / metabolism
-
CD8-Positive T-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / metabolism
-
Cell Differentiation / immunology
-
Cell Lineage / genetics
-
Cell Lineage / immunology
-
Core Binding Factor Alpha 3 Subunit / genetics
-
Core Binding Factor Alpha 3 Subunit / immunology
-
Core Binding Factor Alpha 3 Subunit / metabolism
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / immunology*
-
DNA-Binding Proteins / metabolism
-
Flow Cytometry
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
Oligonucleotide Array Sequence Analysis
-
Th1 Cells / immunology
-
Th1 Cells / metabolism
-
Th2 Cells / immunology
-
Th2 Cells / metabolism
-
Thymus Gland / immunology*
-
Thymus Gland / metabolism
-
Transcription Factors / genetics
-
Transcription Factors / immunology*
-
Transcription Factors / metabolism
-
Transcriptome / immunology
Substances
-
Core Binding Factor Alpha 3 Subunit
-
DNA-Binding Proteins
-
Runx3 protein, mouse
-
Th-POK protein, mouse
-
Transcription Factors
-
Zbtb7a protein, mouse