@article{1781634292a04e12b59a6ccb8a036e6d,
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 RORgt to target genes in differentiating Th17 cells. In addition, we found a strong correlation between IL-17Aproducing CD45RO+CD4 T cells and the expression of ACACA in obese subjects. Thus, ACC1 confers the appropriate function of RORgt through fatty acid synthesis and regulates the obesity-related pathology of Th17 cells.",
author = "Yusuke Endo and Asou, {Hikari K.} and Nao Matsugae and Kiyoshi Hirahara and Kenta Shinoda and Tumes, {Damon J.} and Hirotake Tokuyama and Koutaro Yokote and Toshinori Nakayama",
note = "Funding Information: We thank S.J. Wakil (Baylor College of Medicine) for kindly providing Acaca fl/fl mice and Kaoru Sugaya, Miki Kato, and Toshihiro Ito for their excellent technical assistance. This work was supported by the Global COE Program (Global Center for Education and Research in Immune System Regulation and Treatment) , Japan Science and Technology Agency (JST), CREST , and by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) (Grants-in-Aid for Scientific Research [S] # 26221305 , [B] # 21390147 and # 26293165 , and [C] # 24592083 ; Young Scientists [B] # 24790461 and # 25860352 ; Research Activity start-up # 23890030 and # 25893032 ; Challenging Exploratory Research # 26670362 ; Scientific Research on Innovative Areas “Stem Cell Aging} # 26115009 ); the Ministry of Health, Labor and Welfare ; The Astellas Foundation for Research on Metabolic Disorders ; the Uehara Memorial Foundation ; the Osaka Foundation for Promotion of Fundamental Medical Research ; the Kanae Foundation for the Promotion of Medical Science ; the Princes Takamatsu Cancer Research Fund ; and the Takeda Science Foundation . Publisher Copyright: {\textcopyright} 2015 The Authors.",
year = "2015",
doi = "10.1016/j.celrep.2015.07.014",
language = "English",
volume = "12",
pages = "1042--1055",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}