Abstract
Background: Increased studies indicate that innate lymphoid cells (ILCs) are involved in inflammatory and immune responses in chronic liver injury. However, recruitment and maturation of their subsets during hepatic fibrosis post-HBV infection are unknown. The present study aims to explore the potential impact of ILC precursors (ILCPs) on the modulation of HBV infection-associated fibrosis. Methods: Peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs), chronic hepatitis B infected (CHB), and cirrhotic patients and lymphoid and splenic mononuclear cells from HBV-transgenic mice were isolated to determine the richness of ILC precursors (ILCPs) and ILC subsets by flow cytometry. Results: The richness of ILCPs and ILC3 subsets was significantly increased in PBMCs of patients with chronic hepatitis B infection and in lymph nodes and spleens of HBV-transgenic mice with carbon tetrachloride treatment. Importantly, among these ILCPs, the percentage of CD62L and CXCR6-expressing ILCPs were proportionally enriched. IL-23 may contribute to CD62L+ and CXCR6+ ILCP recruitment and differentiation into ILC3 subsets; whereas a Notch signaling inhibitor DAPT exerted inhibitory effects on them. Conclusion: The microenvironment of HBV infection-associated fibrosis enhances the proliferation, migration, and differentiation of peripheral ILCPs and IIL-23, and Notch signaling pathways may play significant roles in these processes.