title: The transcription factor Jdp2 controls bone homeostasis and antibacterial immunity by regulating osteoclast and neutrophil differentiation.
abstract: Jdp2 is an AP-1 family transcription factor that regulates the epigenetic status of histones. Previous in vitro studies revealed that Jdp2 is involved in osteoclastogenesis. However, the roles of Jdp2 in vivo and its pleiotropic functions are largely unknown. Here we generated Jdp2(-/-) mice and discovered its crucial roles not only in bone metabolism but also in differentiation of neutrophils. Jdp2(-/-) mice exhibited osteopetrosis resulting from impaired osteoclastogenesis. Jdp2(-/-) neutrophils were morphologically normal but had impaired surface expression of Ly6G, bactericidal function, and apoptosis. We also found that ATF3 was an inhibitor of neutrophil differentiation and that Jdp2 directly suppresses its expression via inhibition of histone acetylation. Strikingly, Jdp2(-/-) mice were highly susceptible to Staphylococcus aureus and Candida albicans infection. Thus, Jdp2 plays pivotal roles in in vivo bone homeostasis and host defense by regulating osteoclast and neutrophil differentiation.
authors.affiliation: Laboratory of Host Defense, Osaka University, Osaka, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Maruyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukasaka
authors.forename: Alexis
authors.initials: A
authors.lastname: Vandenbon
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saitoh
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.forename: Kazunari K
authors.initials: KK
authors.lastname: Yokoyama
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kidoya
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
authors.forename: Daron
authors.initials: D
authors.lastname: Standley
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001842:Bone and Bones / Q000276:immunology / Q000378:metabolism*; D002177:Candidiasis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010022:Osteopetrosis / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013203:Staphylococcal Infections / Q000235:genetics
chemical_list: D051700:Activating Transcription Factor 3; D000950:Antigens, Ly; C491386:Jundp2 protein, mouse; C480309:Ly6G antigen, mouse; D012097:Repressor Proteins