title: Obesity Drives Th17 Cell Differentiation by Inducing the Lipid Metabolic Kinase, ACC1.
abstract: Chronic inflammation due to obesity contributes to the development of metabolic diseases, autoimmune diseases, and cancer. Reciprocal interactions between metabolic systems and immune cells have pivotal roles in the pathogenesis of obesity-associated diseases, although the mechanisms regulating obesity-associated inflammatory diseases are still unclear. In the present study, we performed transcriptional profiling of memory phenotype CD4 T cells in high-fat-fed mice and identified acetyl-CoA carboxylase 1 (ACC1, the gene product of Acaca) as an essential regulator of Th17 cell differentiation in vitro and of the pathogenicity of Th17 cells in vivo. ACC1 modulates the DNA binding of RORγt to target genes in differentiating Th17 cells. In addition, we found a strong correlation between IL-17A-producing CD45RO(+)CD4 T cells and the expression of ACACA in obese subjects. Thus, ACC1 confers the appropriate function of RORγt through fatty acid synthesis and regulates the obesity-related pathology of Th17 cells.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hikari K
authors.initials: HK
authors.lastname: Asou
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Matsugae
authors.affiliation: Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Shinoda
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan; South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
authors.forename: Damon J
authors.initials: DJ
authors.lastname: Tumes
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Tokuyama
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan; AMED-CREST, AMED, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan. Electronic address: tnakayama@faculty.chiba-u.jp.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism*
chemical_list: D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; D017493:Leukocyte Common Antigens