title: Naïve T Cell Homeostasis Regulated by Stress Responses and TCR Signaling.
abstract: The survival of naïve T cells is believed to require signals from TCR-pMHC interactions and cytokines such as IL-7. In contrast, signals that negatively impact naïve T cell survival are less understood. We conducted a forward genetic screening of mice and found a mutant mouse line with reduced number of naïve T cells (T-Red mice). T-Red mice have a point mutation in the Kdelr1 gene, and their naïve T cells show enhanced integrated stress response (ISR), which eventually induces their apoptosis. Therefore, naïve T cells require a KDEL receptor-mediated mechanism that efficiently relieves cellular stress for their survival in vivo. Interestingly, naïve T cells expressing TCR with higher affinity/avidity to self-antigens survive in T-Red mice, suggesting the possible link between TCR-mediated survival and ISR-induced apoptosis. In this article, we discuss the regulation of naïve T cell homeostasis, keeping special attention on the ISR and TCR signal.
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamimura
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Atsumi
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University , Sapporo , Japan.
authors.forename: Andrea
authors.initials: A
authors.lastname: Stofkova
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University , Sapporo , Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nishikawa
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Takuto
authors.initials: T
authors.lastname: Ohki
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Hironao
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Kokichi
authors.initials: K
authors.lastname: Katsunuma
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Jiang
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Bando
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Jie
authors.initials: J
authors.lastname: Meng
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Lavannya
authors.initials: L
authors.lastname: Sabharwal
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ogura
authors.affiliation: Osaka University , Suita , Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Arima
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genomic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory of Developmental Immunology, WPI Immunology Frontier Research Center, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
keywords: T cell homeostasis; TCR signaling; mutagenesis; naive T cells; stress response