title: The Anti-Oxidant Ergothioneine Augments the Immunomodulatory Function of TLR Agonists by Direct Action on Macrophages.
abstract: L-Ergothioneine (EGT) is a naturally-occurring amino acid which is characterized by its antioxidant property; yet, the physiological role of EGT has yet to be established. We investigated the immune-enhancing properties of EGT, and found that it acts as a potentiator of toll-like receptor (TLR) signaling. When mouse bone marrow-derived macrophages (BMDMs) were pretreated with EGT, TLR signal-mediated cytokine production was augmented in BMDMs. The results were reproducible with TLR2, 3, 4 and 7 agonists. In particular, IL-6 and IL-12p40 were elevated further by pretreatment with EGT in BMDMs, suggesting the induction of M1 polarization. In co-culture assay with OT-II CD4+ T cells and splenic F4/80+ macrophages, EGT significantly induced Th17 skewing in CD4+ T cells. Thus, EGT is an immune modifier as well as a redox controller under TLR stimulation that induces M1 macrophages and a Th17 shift in inflammation.
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.|Department of Pathology I, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.
authors.forename: Sumito
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shime
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Funami
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Takaki
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.|Department of Pathology I, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology I, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.|Department of Pathology I, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004880:Ergothioneine / Q000494:pharmacology*; D005260:Female; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D000276:Adjuvants, Immunologic; D000975:Antioxidants; D016207:Cytokines; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors; D004880:Ergothioneine