title: Environmental pollutant tributyltin promotes Th2 polarization and exacerbates airway inflammation.
abstract: It has been shown that a relatively high dose of tributyltin (TBT), which is recognized as a particularly notable environmental pollutant, exerts immunotoxic effects such as thymic atrophy via induction of T cell apoptosis. However, the effect of low doses of TBT on the immune responses remains unknown. Here we show that environmentally relevant doses of TBT promoted strong Th2 polarization via suppression and augmentation of Th1 and Th2 development, respectively, from naive CD4(+) T cells primed with anti-CD3 and splenic antigen-presenting cells (APC). TBT-induced Th2 polarization was indirect, working through APC via suppression of IL-12 production by macrophages/DC and the augmentation of IL-10 production by B cells. Th2 polarization was also induced in mice treated with TBT and immunized with OVA or infected with Nippostrongylus brasiliensis. Furthermore, airway inflammation in mice sensitized and challenged with OVA was exacerbated by the administration of TBT with concomitant augmentation of Th2-type immunity. Our results highlight the fact that an important environmental pollutant TBT may present significant risk for the induction of allergic diseases via promotion of Th2 polarization.
authors.affiliation: Department of Bioregulation, Mie University School of Medicine, Tsu, Mie, Japan. katotaku@doc.medic.mie-u.ac.jp
authors.forename: Takuma
authors.initials: T
authors.lastname: Kato
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Uchikawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Yamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Arizono
authors.forename: Saeko
authors.initials: S
authors.lastname: Oikawa
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kawanishi
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishio
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.forename: Kagemasa
authors.initials: K
authors.lastname: Kuribayashi
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D001402:B-Lymphocytes / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects*; D004785:Environmental Pollutants / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D013154:Spleen / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects*; D014220:Trialkyltin Compounds / Q000494:pharmacology*
chemical_list: D004785:Environmental Pollutants; D014220:Trialkyltin Compounds; D016753:Interleukin-10; D018664:Interleukin-12; C011559:tributyltin