The transcription factor Jdp2 controls bone homeostasis and antibacterial immunity by regulating osteoclast and neutrophil differentiation

Immunity. 2012 Dec 14;37(6):1024-36. doi: 10.1016/j.immuni.2012.08.022. Epub 2012 Nov 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 3 / genetics
  • Activating Transcription Factor 3 / metabolism
  • Animals
  • Antigens, Ly / genetics
  • Antigens, Ly / metabolism
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Bone and Bones / immunology
  • Bone and Bones / metabolism*
  • Candidiasis / genetics
  • Cell Differentiation / genetics
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Homeostasis
  • Mice
  • Mice, Knockout
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism
  • Osteopetrosis / genetics
  • Osteopetrosis / immunology
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Staphylococcal Infections / genetics


  • Activating Transcription Factor 3
  • Antigens, Ly
  • Jundp2 protein, mouse
  • Ly6G antigen, mouse
  • Repressor Proteins

Associated data

  • GEO/GSE42063