Obesity Drives Th17 Cell Differentiation by Inducing the Lipid Metabolic Kinase, ACC1

被引：203

作者：

Endo, Yusuke ^{[1
]}

Asou, Hikari K. ^{[1
]}

Matsugae, Nao ^{[1
]}

Hirahara, Kiyoshi ^{[2
]}

Shinoda, Kenta ^{[1
]}

Tumes, Damon J. ^{[1
,5
]}

Tokuyama, Hirotake ^{[3
]}

Yokote, Koutaro ^{[3
]}

Nakayama, Toshinori ^{[1
,4
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Immunol, Chuo Ku, Chiba 2608670, Japan

[2] Chiba Univ, Grad Sch Med, Dept Adv Allergol Airway, Chuo Ku, Chiba 2608670, Japan

[3] Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chuo Ku, Chiba 2608670, Japan

[4] AMED, CREST, Chuo Ku, Chiba 2608670, Japan

[5] South Australian Hlth & Med Res Inst, Adelaide, SA 5000, Australia

来源：

CELL REPORTS | 2015年 / 12卷 / 06期

基金：

日本科学技术振兴机构;

关键词：

ACETYL-COA CARBOXYLASE-1; INNATE LYMPHOID-CELLS; T-CELLS; TRANSCRIPTION FACTOR; INSULIN-RESISTANCE; REGULATORY T; T(H)17; NETWORK; ACCUMULATION; AUTOIMMUNITY;

D O I：

10.1016/j.celrep.2015.07.014

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 acetylCoA 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 ROR gamma t 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 ROR gamma t through fatty acid synthesis and regulates the obesity-related pathology of Th17 cells.

引用

页码：1042 / 1055

页数：14

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