title: Zinc-binding metallothioneins are key modulators of IL-4 production by basophils.
abstract: Zinc (Zn) is an essential nutrient, and Zn deficiency causes immunodeficiency and skin disorders. Basophils express FcɛRI on their surface and release multiple mediators after receptor cross-linking, including large amounts of IL-4. However, the mechanisms involved in the FcɛRI-mediated regulation of basophil IL-4 production are currently unclear. Here, we show that the Zn-binding metallothionein (MT) proteins are essential for the FcɛRI-induced basophil production of IL-4. Basophils from MT-I/II(-/-) mice produced significantly less FcɛRI-induced IL-4 than did wild-type basophils. The MTs were involved in maintaining intracellular Zn levels, thereby regulated the calcineurin activity and nuclear factor of activated T-cell (NFAT)-mediated IL-4 production. These results suggest that the MT-dependent control of Zn homeostasis is a novel mechanism for regulating basophil IL-4 production.
authors: Department of Dermatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Laboratory for Homeostatic Network, RIKEN Research Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Tsukasa
authors: T
authors: Ugajin
authors: Laboratory for Homeostatic Network, RIKEN Research Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Laboratory of Immune Regulation, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka, Mie 513-8670, Japan. Electronic address: nishida@rcai.riken.jp.
authors: Keigo
authors: K
authors: Nishida
authors: Laboratory for Homeostatic Network, RIKEN Research Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Satoru
authors: S
authors: Yamasaki
authors: Center for Environmental Risk Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
authors: Junko
authors: J
authors: Suzuki
authors: Laboratory Animal Research Center, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Masaharu
authors: M
authors: Mita
authors: Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan; Laboratory for Cytokine Regulation, RIKEN Research Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Masato
authors: M
authors: Kubo
authors: Department of Dermatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors: Hiroo
authors: H
authors: Yokozeki
authors: Osaka University, 1-1 Yamada-oka, Suita, Osaka 565-0871, Japan. Electronic address: hirano@hq.osaka-u.ac.jp.
authors: Toshio
authors: T
authors: Hirano
mesh_terms: D000818:Animals; D001491:Basophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019703:Calcineurin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008668:Metallothionein / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D061251:Primary Cell Culture; D011485:Protein Binding; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D015032:Zinc / Q000276:immunology* / Q000378:metabolism
chemical_list: C491054:Mt2 protein, mouse; D050778:NFATC Transcription Factors; D017455:Receptors, IgE; C525355:metallothionein-1, mouse; D015847:Interleukin-4; D008668:Metallothionein; D019703:Calcineurin; D015032:Zinc
keywords: Basophil; IL-4 signal transduction; Metallothionein; Zinc