Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development
- Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):11780-5. doi: 10.1073/pnas.1323549111.
- 1. Laboratory for Immune Regeneration,Graduate School of Frontier Biosciences, Osaka University, Yamada-oka, Suita, Osaka 565-0871, Japan;
- 2. Laboratory for Homeostatic Network,Osteoimmunology, Deutsches Rheuma-Forschungszentrum, Berlin, Charitéplatz, 10117 Berlin, Germany;
- 3. Laboratory for Immune Regeneration.
- 4. Laboratory for Immunotherapy.
- 5. Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Hatanodai, Shinagawa, Tokyo 142-8555, Japan;
- 6. Laboratory of Developmental Immunology, Graduate School of Medicine.
- 7. Nagahama Institute of Bio-Science and Technology, Tamura, Nagahama, Shiga 526-0829, Japan;
- 8. Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Hatanodai, Shinagawa, Tokyo 142-8555, Japan;Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin 446-729, Republic of Korea;
- 9. Laboratory for Immunogenetics.
- 10. Department of Veterinary Physiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan; and.
- 11. Department of Human Genome Research, Kazusa DNA Research Institute, Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan.
- 12. Department of Human Genome Research, Kazusa DNA Research Institute, Kazusa-kamatari, Kisarazu, Chiba 292-0818, JapanLaboratory for Integrative Genomics, and.
- 13. Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan;
- 14. Laboratory for Homeostatic Network,Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Hatanodai, Shinagawa, Tokyo 142-8555, Japan; [email protected].
The immune system is influenced by the vital zinc (Zn) status, and Zn deficiency triggers lymphopenia; however, the mechanisms underlying Zn-mediated lymphocyte maintenance remain elusive. Here we investigated ZIP10, a Zn transporter expressed in the early B-cell developmental process. Genetic ablation of Zip10 in early B-cell stages resulted in significant reductions in B-cell populations, and the inducible deletion of Zip10 in pro-B cells increased the Caspase activity in parallel with a decrease in intracellular Zn levels. Similarly, the depletion of intracellular Zn by a chemical chelator resulted in spontaneous Caspase activation leading to cell death. Collectively, these findings indicated that ZIP10-mediated Zn homeostasis is essential for early B-cell survival. Moreover, we found that ZIP10 expression was regulated by JAK-STAT pathways, and its expression was correlated with STAT activation in human B-cell lymphoma, indicating that the JAK-STAT-ZIP10-Zn signaling axis influences the B-cell homeostasis. Our results establish a role of ZIP10 in cell survival during early B-cell development, and underscore the importance of Zn homeostasis in immune system maintenance.