Oral administration of PEGylated TLR7 ligand ameliorates alcohol-associated liver disease via the induction of IL-22
Qinglan Wang, So Yeon Kim, Hiroshi Matsushita, Zhijun Wang, Vijay Pandyarajan, Michitaka Matsuda, Koichiro Ohashi, Takashi Tsuchiya, Yoon Seok Roh, Calvin Kiani, Yutong Zhao, Michael Chan, Suzanne Devkota, Shelly C. Lu, Tomoko Hayashi, Dennis A. Carson, Ekihiro Seki
Abstract
Significance Alcoholic hepatitis (AH) is a severe form of alcohol-associated liver disease (ALD) that is characterized by chronic liver injury and inflammation. The current treatment strategy for AH involves the use of corticosteroids, despite a lack of evidence supporting their efficacy, because other effective therapeutic agents are not available. Here, we demonstrate that activation of TLR7 signaling via the oral administration of 1Z1, which is a synthetic TLR7 ligand that does not elicit systemic side effects, protects against liver injury in an AH mouse model. The therapeutic effect of 1Z1 requires TLR7 expression and is mediated by intestinal IL-22 upregulation. Our study suggests that 1Z1-induced TLR7 activation and IL-22 induction may be a therapeutic approach for the treatment of AH.