title: Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation.
abstract: Natural killer cells belong to the family of innate lymphoid cells comprising the frontline defense against infected and transformed cells. Development and activation of natural killer cells is highly dependent on interleukin-15 signaling. However, very little is known about the transcription program driving this process. The transcription factor Runx3 is highly expressed in natural killer cells, but its function in these cells is largely unknown. We show that loss of Runx3 impaired interleukin-15-dependent accumulation of mature natural killer cells in vivo and under culture conditions and pregnant Runx3(-/-) mice completely lack the unique population of interleukin-15-dependent uterine natural killer cells. Combined chromatin immunoprecipitation sequencing and differential gene expression analysis of wild-type versus Runx3-deficient in vivo activated splenic natural killer cells revealed that Runx3 cooperates with ETS and T-box transcription factors to drive the interleukin-15-mediated transcription program during activation of these cells. Runx3 functions as a nuclear regulator during interleukin-15-dependent activation of natural killer cells by regulating the expression of genes involved in proliferation, maturation, and migration. Similar studies with additional transcription factors will allow the construction of a more detailed transcriptional network that controls natural killer cell development and function.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ditsa
authors.initials: D
authors.lastname: Levanon
authors.forename: Varda
authors.initials: V
authors.lastname: Negreanu
authors.forename: Joseph
authors.initials: J
authors.lastname: Lotem
authors.forename: Karen Rae
authors.initials: KR
authors.lastname: Bone
authors.forename: Ori
authors.initials: O
authors.lastname: Brenner
authors.forename: Dena
authors.initials: D
authors.lastname: Leshkowitz
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000378:metabolism; D005260:Female; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D000953:Antigens, Protozoan; D050677:Core Binding Factor Alpha 3 Subunit; D019409:Interleukin-15; D007376:Interleukin-2; C493730:Runx3 protein, mouse; D014157:Transcription Factors; C061194:Eimeria tenella sporozoite antigen