Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development
- 29 July 2014
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 111 (32), 11780-11785
- https://doi.org/10.1073/pnas.1323549111
Abstract
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.Keywords
This publication has 48 references indexed in Scilit:
- ZIP8 Regulates Host Defense through Zinc-Mediated Inhibition of NF-κBCell Reports, 2013
- Pathogenesis of follicular lymphomaJCI Insight, 2012
- The role of STAT5 in lymphocyte development and transformationCurrent Opinion in Immunology, 2012
- Regulation of T cell receptor signaling by activation-induced zinc influxThe Journal of Experimental Medicine, 2011
- BCL6 is critical for the development of a diverse primary B cell repertoireThe Journal of Experimental Medicine, 2010
- Zinc transporter Znt5/Slc30a5 is required for the mast cell–mediated delayed-type allergic reaction but not the immediate-type reactionThe Journal of Experimental Medicine, 2009
- The Zinc Transporter SLC39A13/ZIP13 Is Required for Connective Tissue Development; Its Involvement in BMP/TGF-β Signaling PathwaysPLOS ONE, 2008
- Spondylocheiro Dysplastic Form of the Ehlers-Danlos Syndrome—An Autosomal-Recessive Entity Caused by Mutations in the Zinc Transporter Gene SLC39A13American Journal of Human Genetics, 2008
- Protein tyrosine phosphatases: from genes, to function, to diseaseNature Reviews Molecular Cell Biology, 2006
- Testing gene function early in the B cell lineage in mb1-cre miceProceedings of the National Academy of Sciences of the United States of America, 2006