title: Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis.
abstract: The RUNX transcription factors are important regulators of lineage-specific gene expression. RUNX are bifunctional, acting both as activators and repressors of tissue-specific target genes. Recently, we have demonstrated that Runx3 is a neurogenic transcription factor, which regulates development and survival of proprioceptive neurons in dorsal root ganglia. Here we report that Runx3 and Runx1 are highly expressed in thymic medulla and cortex, respectively, and function in development of CD8 T cells during thymopoiesis. Runx3-deficient (Runx3 KO) mice display abnormalities in CD4 expression during lineage decisions and impairment of CD8 T cell maturation in the thymus. A large proportion of Runx3 KO peripheral CD8 T cells also expressed CD4, and in contrast to wild-type, their proliferation ability was largely reduced. In addition, the in vitro cytotoxic activity of alloimmunized peritoneal exudate lymphocytes was significantly lower in Runx3 KO compared with WT mice. In a compound mutant mouse, null for Runx3 and heterozygous for Runx1 (Runx3-/-;Runx1+/-), all peripheral CD8 T cells also expressed CD4, resulting in a complete lack of single-positive CD8+ T cells in the spleen. The results provide information on the role of Runx3 and Runx1 in thymopoiesis and suggest that both act as transcriptional repressors of CD4 expression during T cell lineage decisions.
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Eilon
authors.initials: E
authors.lastname: Woolf
authors.forename: Cuiying
authors.initials: C
authors.lastname: Xiao
authors.forename: Ofer
authors.initials: O
authors.lastname: Fainaru
authors.forename: Joseph
authors.initials: J
authors.lastname: Lotem
authors.forename: Dalia
authors.initials: D
authors.lastname: Rosen
authors.forename: Varda
authors.initials: V
authors.lastname: Negreanu
authors.forename: Yael
authors.initials: Y
authors.lastname: Bernstein
authors.forename: Dalia
authors.initials: D
authors.lastname: Goldenberg
authors.forename: Ori
authors.initials: O
authors.lastname: Brenner
authors.forename: Gideon
authors.initials: G
authors.lastname: Berke
authors.forename: Ditsa
authors.initials: D
authors.lastname: Levanon
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002455:Cell Division; D019070:Cell Lineage; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000502:physiology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493726:Runx1 protein, mouse; C493730:Runx3 protein, mouse; D014157:Transcription Factors