title: Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development.
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.
authors: Laboratory for Immune Regeneration,Graduate School of Frontier Biosciences, Osaka University, Yamada-oka, Suita, Osaka 565-0871, Japan;
authors: Tomohiro
authors: T
authors: Miyai
authors: Laboratory for Homeostatic Network,Osteoimmunology, Deutsches Rheuma-Forschungszentrum, Berlin, Charitéplatz, 10117 Berlin, Germany;
authors: Shintaro
authors: S
authors: Hojyo
authors: Laboratory for Immune Regeneration.
authors: Tomokatsu
authors: T
authors: Ikawa
authors: Laboratory for Immunotherapy.
authors: Masami
authors: M
authors: Kawamura
authors: Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Hatanodai, Shinagawa, Tokyo 142-8555, Japan;
authors: Tarou
authors: T
authors: Irié
authors: Laboratory of Developmental Immunology, Graduate School of Medicine.
authors: Hideki
authors: H
authors: Ogura
authors: Nagahama Institute of Bio-Science and Technology, Tamura, Nagahama, Shiga 526-0829, Japan;
authors: Atsushi
authors: A
authors: Hijikata
authors: 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;
authors: Bum-Ho
authors: BH
authors: Bin
authors: Laboratory for Immunogenetics.
authors: Takuwa
authors: T
authors: Yasuda
authors: Department of Veterinary Physiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan; and.
authors: Hiroshi
authors: H
authors: Kitamura
authors: Department of Human Genome Research, Kazusa DNA Research Institute, Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan.
authors: Manabu
authors: M
authors: Nakayama
authors: Department of Human Genome Research, Kazusa DNA Research Institute, Kazusa-kamatari, Kisarazu, Chiba 292-0818, JapanLaboratory for Integrative Genomics, and.
authors: Osamu
authors: O
authors: Ohara
authors: Laboratory for Immunogenetics.
authors: Hisahiro
authors: H
authors: Yoshida
authors: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan;
authors: Haruhiko
authors: H
authors: Koseki
authors: Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Hatanodai, Shinagawa, Tokyo 142-8555, Japan;
authors: Kenji
authors: K
authors: Mishima
authors: Laboratory for Homeostatic Network,Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Hatanodai, Shinagawa, Tokyo 142-8555, Japan; fukada@rcai.riken.jp.
authors: Toshiyuki
authors: T
authors: Fukada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D027682:Cation Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008231:Lymphopenia / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D016207:Cytokines; C519886:SLC39A10 protein, human; D050791:STAT Transcription Factors; C557566:ZIP10 protein, mouse; D053612:Janus Kinases; D020169:Caspases; D015032:Zinc
keywords: B-lymphocyte; apoptosis; bone marrow; cytokine; zinc-signaling axis