title: Lipid mediators foster the differentiation of T follicular helper cells.
abstract: Lipid mediators such as leukotrienes and lipoxines broadly regulate innate and acquired immunity, and their dysfunction causes various immune-mediated disorders. We previously reported a salient feature of arachidonate 5-lipoxyganase (Alox5), which is responsible for the production of such lipid mediators, in the regulation of high affinity antibodies in vivo. The aim of this study was to determine the functional significance of Alox5-related lipid mediators during the processes of acquired humoral responses. The results of in vitro experiments using lymphocytes in tonsils and blood specimens showed that lipoxin A4 (LXA4) and leukotriene B4 (LTB4) have the capacity to differentiate naïve CD4+T cells into T follicular helper (Tfh) cells, which activate naïve B cells to form germinal centers. Such a function of LXA4 was further supported by results of in vitro studies using BML-111 and BOC-2, which are an agonist and an antagonist, respectively, of FPR2 of an LXA4-specific cell-surface receptor. The results suggest that such lipid mediators have a potential role in the development of lymphoid follicles through the regulation of Tfh cell differentiation.
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nagaya
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawata
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kamekura
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Sumito
authors.initials: S
authors.lastname: Jitsukawa
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Motonari
authors.initials: M
authors.lastname: Kamei
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ogasawara
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Takano
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
authors.affiliation: Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan. Electronic address: ichimiya@sapmed.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Ichimiya
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism / Q000494:pharmacology; D050356:Lipid Metabolism; D008055:Lipids / Q000494:pharmacology; D044045:Lipoxins / Q000378:metabolism / Q000494:pharmacology; D018077:Receptors, Leukotriene / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D015289:Leukotrienes; D008055:Lipids; D044045:Lipoxins; D018077:Receptors, Leukotriene; C040527:lipoxin A4; D001094:Arachidonate 5-Lipoxygenase; C583212:ALOX5 protein, human
keywords: Lipid mediators; T follicular helper cells