DC-SIGN+ Macrophages alleviates Non-Alcoholic Steatohepatitis by modulating inflammatory cytokine secretion

The modulation of immune responses by innate immune receptors plays a pivotal role in the progression of non-alcoholic steatohepatitis (NASH). In this study, we aim to comprehensively dissect the involvement of the C-type lectin receptor DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) in NASH progression. RNA sequencing was conducted on liver samples obtained from mice fed either a control diet or a HFHC diet inducing NASH for 16 weeks. At 8 weeks post feeding, animals were transduced via tail vein with Adeno-Associated Virus 9 (AAV9) expressing CD68 promoter-driven human DC-SIGN (hDC-SIGN) or GFP control. Data obtained from the transcriptomic profiles indicated that macrophage-specific delivery of hDC-SIGN strongly attenuated liver metabolic and inflammatory abnormalities, leading to the amelioration of NASH progression.