The Transcription Factor Jdp2 Controls Bone Homeostasis and Antibacterial Immunity by Regulating Osteoclast and Neutrophil Differentiation

Maruyama, K. et al. 2012. Immunity. 37, 1024-1036

Speaker: Yi-Dan Ou (歐懿丹)                                     Time: 13:10~14:00, May. 22, 2013

Commentator: Dr. Lien-I Hor (何漣漪 博士)          

Time: 13:10~14:00, May. 22, 2013

Place: Room 601

Abstract:

      The transcription factor Jun dimerization protein 2 (Jdp2) is a member of activator protein 1 (AP-1) family and as a transcriptional repressor of other AP-1 component. Previous studies revealed that Jdp2 is involved in a variety of cellular responses such as UV-induced apoptosis, cell differentiation and tumorigenesis. Furthermore, Jdp2 is a positive regulator ofosteoclastogenesis in vitro (1). Hypomethylation of the Jdp2 promoter in common myeloid progenitors and granulocyte-macrophage progenitors has led to suggestions that Jdp2 participates in the differentiation of myeloid cells (2). However, the roles of Jdp2 in vivo and its pleiotropic functions are largely unknown. In this study, the authors demonstrated that Jdp2 regulates not only bone metabolism but also neutrophil differentiation in vivo. The authors used qPCR analysis and found that Jdp2 mRNA expression was higher in osteoclasts and neutrophils than in other cells. To evaluate osteoclastogenesis in vivo, they generated Jdp2^-/- mice. Radiographic analysis of the femurs showed that Jdp2^-/- mice had osteopetrosis. Jdp2 is involved in differentiation of myeloid cells (2)[u1] . Besides, the authors also discovered Jdp2 mRNA was highly expressed in neutrophil[u2] . The authors used flow cytometry analysis to check the maturity in Jdp2^-/-neutrophils and investigated the neutrophil functions under bacterial infections.[u3]  In Jdp2^-/- neutrophils, the morphology was normal; whereas, Ly6G expression, apoptosis and bactericidal function were impaired. However, these abnormalities in Jdp2^-/- neutrophils arises in the late differentiation phase[u4]  and can be corrected by re-expression of Jdp2.[m5]  It has been reported that activating transcription factor 3 (ATF3) expression is suppressed by Jdp2 in fibroblasts (3). The author used ChIP-sequencing technique to find that the Jdp2 overexpressed in wild-type neutrophils suppressed ATF3 promoter acetylation. As a result of impaired bactericidal function in Jdp2^-/- neutrophils, the authors checked the susceptibility of Jdp2^-/- mice to bacterial and fungal. Results show that Jdp2^-/- mice were highly susceptible to S. aureus infection. Taken together, Jdp2 plays crucial roles in bone homeostasis and host defense by regulating osteoclast and neutrophil differentiation in vivo.

References:

1.   Kawaida R. et al. 2003. Jun dimerization protein 2 (JDP2), a member of the AP-1 family of transcription factor, mediates osteoclast differentiation induced by RANKL. The Journal of experimental medicine 197:1029-35

2.   Ji H. et al. 2010. Comprehensive methylome map of lineage commitment from haematopoietic progenitors. Nature 467:338-42

3.   Weidenfeld-Baranboim K. et al. 2009. The ubiquitously expressed bZIP inhibitor, JDP2, suppresses the transcription of its homologue immediate early gene counterpart, ATF3. Nucleic acids research 37:2194-203