title: HOXB9 acts as a negative regulator of activated human T cells in response to amino acid deficiency.
abstract: T-cell activation is an energy expenditure process and should be properly controlled in accordance with the availability of nutrients such as amino acids to eliminate wasteful energy consumption. However, the details of response to amino acids insufficiency in activated T cells remain largely unknown. Here we show that homeobox B9 (HOXB9), a member of the homeobox gene family that is known as a morphogenesis regulator, acts as a suppressor of activated human T cells to address amino acid starvation. The expression of HOXB9 was triggered by amino acid deprivation as well as functional inhibition of L-type amino acid transporter 1 (also known as SLC7A5) via activating transcription factor 4 in activated T cells. HOXB9 interfered the activities of NF-κB, nuclear factor of activated T-cells (NFAT) and AP-1 but not retinoic acid receptor-related orphan receptor, resulting in attenuation of the production of selective cytokines in activated T cells. Thus, the morphogenetic gene plays an unexpected role in the regulation of cellular metabolism with changes in the nutrition status in human T cells.
authors.affiliation: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
authors.forename: Motoshi
authors.initials: M
authors.lastname: Ouchi
authors.affiliation: J-Pharma Co, Ltd, Kanagawa, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endou
authors.affiliation: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Anzai
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000596:Amino Acids / Q000172:deficiency*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C497109:ATF4 protein, human; D000596:Amino Acids; C491257:HOXB9 protein, human; D018398:Homeodomain Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D018168:Receptors, Retinoic Acid; D018808:Transcription Factor AP-1; D051701:Activating Transcription Factor 4