Proliferation, migration, and differentiation of circulating ILC precursors in HBV infection-associated fibrosis

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.

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.

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.

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.