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A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells.

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.

SUBMITTER: Vacchio MS

PROVIDER: S-EPMC4251968 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells.

Vacchio Melanie S MS Wang Lie L Bouladoux Nicolas N Carpenter Andrea C AC Xiong Yumei Y Williams Linus C LC Wohlfert Elizabeth E Song Ki-Duk KD Belkaid Yasmine Y Love Paul E PE Bosselut Rémy R

Nature immunology 20140817 10

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 ...[more]

PMID: 25129370

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