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

• A high-fat diet augments Th17 cell development and the expression of Acaca
• ACC1 controls Th17 cell development in vitro and Th17 cell pathogenicity in vivo
• ACC1 modulates RORγt function in developing Th17 cells
• Obesity in humans induces ACACA and IL-17A expression in CD4 T cells

SummaryChronic 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.

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