Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength

Hojyo, Shintaro; Miyai, Tomohiro; Fujishiro, Hitomi; Kawamura, Masami; Yasuda, Tomohiko; Hijikata, Atsushi; Bin, Bum-Ho; Irié, Tarou; Tanaka, Junichi; Atsumi, Toru; Murakami, Masaaki; Nakayama, Manabu; Ohara, Osamu; Himeno, Seiichiro; Yoshida, Hisahiro; Koseki, Haruhiko; Ikawa, Tomokatsu; Mishima, Kenji; Fukada, Toshiyuki

doi:10.1073/pnas.1323557111

Cited by 105 publications

(91 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, we also found that ZIP10 has an important role in the humoral immune response mediated by mature B cells (21), indicating that ZIP10 has unique functions in both early and mature B-cell populations by regulating different molecular and cellular events. Our studies on ZIP10 in B cells provide new insight into the relevance of Zn signaling in immuno-physiological events.…”

Section: Discussionmentioning

confidence: 64%

See 1 more Smart Citation

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

Miyai

Hojyo

Ikawa³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

106

View full text Add to dashboard Cite

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.B-lymphocyte | apoptosis | cytokine | bone marrow | zinc-signaling axis

show abstract

Section: Discussionmentioning

confidence: 64%

“…S2B) on which it was glycosylated and formed oligomers (Figs. S1C and S3) (20,21). Based on these findings but lacking evidence for immuno-physiological roles of ZIP10 in vivo, we first investigated whether ZIP10 plays a role in B-cell development by generating Zip10…”

Section: Resultsmentioning

confidence: 99%

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

Miyai

Hojyo

Ikawa³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

106

View full text Add to dashboard Cite

show abstract

“…Inflammatory T-cell behavior in animals infected with T. cruzi is also tightly regulated by a network of B cells, once the clearance of an established infection requires a successful humoral response [22]. Zinc deficiency is associated with several immune adverse effects, compromising cellular and humoral response [23]. Zinc levels are highly dependent on tissue stocks, once serum Zn is only a small percentage (0.1%) of whole-body-mass Zn content [24].…”

Section: Discussionmentioning

confidence: 99%

Chagas disease control and role of zinc supplementation in pregnancy

Costa

Pereira

Barbosa

et al. 2017

Matters

View full text Add to dashboard Cite

During normal pregnancy, some changes in cell numbers, phenotype, and activity take place. The impairment of maternal immune function in the course of pregnancy contributes to a decreased resistance against several pathogens. Since scarce data concerning the effects of maternal zinc supplementation during infection are available, the purpose of our current study was to evaluate immune response alterations and zinc levels in pregnant T. cruzi-infected Wistar rats under zinc therapy. Pregnant Wistar rats were used in all experiments. TCD3 + CD4 + , TCD3 + CD8 + , B cells (CD45RA + ), splenocyte proliferation, and plasma zinc levels were measured at 14 th day after infection (18 th day of pregnancy). High proportions of T-and B-cells were found in infected pregnant and zinc-treated animals as compared to pregnant infected and untreated counterparts. Moreover, zinc plasmatic levels from supplemented animals were similar to the non-infected/non-supplemented group. These findings demonstrate that dietary zinc supplementation throughout pregnancy improves immune response during T. cruzi infection. These results will base further methods to use zinc in pregnant women affected by T. cruzi.

show abstract

“…Zinc acts as an intracellular second messenger to facilitate certain signaling events [5] . Compelling evidence suggests that zinc signal from zinc transporter controls the organ-specific functions such as connective tissue development [6] , systemic growth [7] , and immune regulation [8,9] . Thus, zinc signaling is one of the emerging factors in regulation of physiological and pathological events.…”

Section: Research Highlightmentioning

confidence: 99%

Emerging role of zinc homeostasis by zinc transporter ZIP7 in intestinal homeostatic self-renewal

2017

Inflamm Cell Signal

View full text Add to dashboard Cite

There has been a growing interest in the biological significance of zinc and its regulatory mechanism in the development of tissue and in the maintenance of tissue homeostasis. The intestinal epithelium undergoes a continuous self-renewing process to maintain the intestinal homeostasis. Moreover, dysregulation of this process often causes various intestinal disorders including inflammatory bowel disease, ulcer, and cancer. However, the molecular basis of zinc-dependent regulation of intestinal epithelial cell turnover is not fully understood. In this research highlight, we describe that the zinc transporter ZIP7 (highly expressed in undifferentiated epithelial cells) plays a critical role in the intestinal epithelial self-renewal process by alleviating the ER stress during vigorous proliferative response. Our findings also provide evidence showing that the fine-tuning of intracellular zinc homeostasis by ZIP7 is essential to maintain epithelial homeostasis in the intestine.

show abstract

Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength

Cited by 105 publications

References 43 publications

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

Chagas disease control and role of zinc supplementation in pregnancy

Emerging role of zinc homeostasis by zinc transporter ZIP7 in intestinal homeostatic self-renewal

Contact Info

Product

Resources

About