Mus musculus strain:C57BL6/J Raw sequence reads. Mus musculus strain:C57BL6/J

Limited understanding of key pathogenic mechanisms is largely attributed for the lack of widely effective therapies to NAFLD. Obesity-driven modulation of the inflammatory environment and activation of the Th17 axis play a central role in NAFLD pathogenesis. However, the characteristics and mechanisms underlying the pathogenic potential of Th17 cells in NAFLD remain unknown. Here, we demonstrate that NAFLD progression is associated with polarization and accumulation of a unique population of inflammatory hepatic CXCR3+Th17 cells (ihTh17) in mice. Transfer of ihTh17 cells accelerated and exacerbated NAFLD pathogenesis in vivo. ihTh17 cells, compared to conventional CXCR3-Th17 cells, exhibited increased open chromatin marks in enhancer regions, increased metabolic capacity, and were able to simultaneously produce an array of proinflammatory cytokines which directly contributed to hepatocellular damage.