title: 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.
authors.affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Vacchio
authors.affiliation: 1] Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2].
authors.forename: Lie
authors.initials: L
authors.lastname: Wang
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Carpenter
authors.affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Linus C
authors.initials: LC
authors.lastname: Williams
authors.affiliation: 1] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. [2].
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wohlfert
authors.affiliation: 1] Section on Cellular and Developmental Biology, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. [2].
authors.forename: Ki-Duk
authors.initials: KD
authors.lastname: Song
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.affiliation: Section on Cellular and Developmental Biology, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Love
authors.affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Rémy
authors.initials: R
authors.lastname: Bosselut
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000276:immunology
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C493730:Runx3 protein, mouse; C497211:Zbtb7b protein, mouse; C117093:Zbtb7a protein, mouse