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. Epub 2014 Jul 29.


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: B-lymphocyte; apoptosis; bone marrow; cytokine; zinc-signaling axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Caspases / metabolism
  • Cation Transport Proteins / deficiency
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / immunology*
  • Cell Differentiation
  • Cell Survival / immunology
  • Cytokines / metabolism
  • Homeostasis
  • Humans
  • Janus Kinases / metabolism
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Lymphopenia / etiology
  • Lymphopenia / immunology
  • Lymphopenia / metabolism
  • Mice
  • Mice, Knockout
  • Models, Immunological
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Zinc / deficiency
  • Zinc / metabolism*


  • Cation Transport Proteins
  • Cytokines
  • SLC39A10 protein, human
  • STAT Transcription Factors
  • ZIP10 protein, mouse
  • Janus Kinases
  • Caspases
  • Zinc