Type I interferon upregulates IL-18RAP in neutrophils to enhance chemotaxis and bactericidal activity in autoimmune liver diseases.

OBJECTIVE

Given the established association of interleukin-18 (IL-18) and IL-18 receptor accessory protein (IL-18RAP) with autoimmune liver diseases (AILD), while their specific mechanism remains unclear, this study aimed to investigate the expression and functional significance of IL-18RAP in neutrophils from patients with AILD.

METHODS

The expression levels of IL-18RAP were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Serum type I interferon (IFN) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). In vitro cell experiments were conducted to assess chemotactic phagocytosis and to analyze the regulatory effect of IL-18RAP on neutrophil function. In vitro IFN stimulation experiments were performed to analyze the relationship between IL-18RAP expression and type I IFN.

RESULTS

IL-18RAP mRNA and protein expression levels were increased in patients with AILD. After IL-18 stimulation, the chemotaxis index and nitroblue tetrazolium (NBT) reduction rate of neutrophils in the AILD group increased (P < 0.05). Serum type I IFN concentrations were elevated in AILD patients (Z = -2.14, P = 0.032). IL-18RAP mRNA expression was upregulated in the group stimulated with high-concentration patient serum and in the human recombinant IFN-α stimulation group, indicating that high concentrations of type I IFN can upregulate IL-18RAP expression in neutrophils.

CONCLUSION

Elevated IL-18RAP expression in AILD patients enhanced the chemotactic, phagocytic, and bactericidal functions of neutrophils. Higher serum type I IFN levels in AILD patients upregulated IL-18RAP expression in neutrophils, suggesting that type I IFN contributes to the pathogenesis of AILD by upregulating IL-18RAP.