Innate lymphoid cell subsets in the pathogenesis of primary biliary cholangitis

Abstract

Background and aim: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by destructive lymphocytic cholangitis and specific anti-mitochondrial antibodies. Innate lymphoid cells (ILCs) have been reported to play a role in liver homeostasis and autoimmunity.

Methods: We evaluated the features of peripheral ILC1s and ILC3 in patients with PBC and hepatic ILC1 and ILC3 in two different PBC mouse models (dominant-negative transforming growth factor-beta receptor II [dnTGFβRII] and 2-octynoic acid-bovine serum albumin [2OA-BSA]).

Results: A total of 115 patients and 18 healthy controls were enrolled in the study. Decreased circulating ILC1/3s were observed in early-stage PBC patients, and the numbers of ILC1/3s were negatively correlated with specific parameters and the proportion of T-helper (Th) 1 and Th17 cells. Reduced numbers of ILC1s were observed in PBC mouse models with different etiologies. ILC1-deficient mice had more severe hepatic inflammation after inducing the 2OA-BSA model. Continuous low-dose injections of lipopolysaccharide (LPS) reduced ILC1 levels in mice, consistent with the lower level of ILC1s in PBC patients with high LPS (> 50 ng/mL), and aggravated hepatic lymphocyte infiltration.

Conclusion: Patients with PBC had decreased ILC1s, which were negatively correlated with CD4⁺ T cells. Deficient ILC1 populations led to disease exacerbations in mice. Our results indicated that ILC1s may participate in the pathogenesis of PBC.

Keywords: etiology; immune tolerance; innate lymphoid cells; primary biliary cholangitis.