期刊
CELLS
卷 10, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/cells10050964
关键词
SLE; interleukin-18 receptor accessory protein; type I interferon; cellular function
类别
资金
- Health and Medical Research Fund of the Hong Kong Government [06172386]
The study found that IL18RAP expression is elevated in neutrophils of SLE patients, especially those with a history of nephritis, and is associated with disease activity and immunological manifestations. Neutrophils from SLE patients exhibit higher IL-18-mediated reactive oxygen species generation, which may be attributed to the upregulation of IL18RAP expression.
Interleukin-18 receptor accessory protein (IL18RAP) is an indispensable subunit for the IL-18 receptor (IL-18R) complex's ability to mediate high-affinity IL-18 binding and signalling transduction. Interest in IL-18 in systemic lupus erythematosus (SLE) has been mostly focused on its role as a type 1 T helper cell-driving cytokine. The functional significance of IL18RAP in mediating the IL-18-driven response in myeloid cells in SLE remains largely unexplored. This study aimed to investigate the expression and function significance of IL18RAP in neutrophils of SLE patients. By qRT-PCR and Western blot analyses, elevated expressions of IL18RAP mRNA and protein were observed in neutrophils from SLE patients-particularly those with a history of nephritis. IL18RAP expression correlated negatively with complement 3 level and positively with disease activity, with higher expression in patients exhibiting renal and immunological manifestations. The increased IL18RAP expression in SLE neutrophils could be attributed to elevated type I interferon level in sera. Functionally, neutrophils from SLE patients showed higher IL-18-mediated enhancement in reactive oxygen species (ROS) generation, which showed positive correlation with IL18RAP expression and could be neutralized by anti-IL18RAP blocking antibodies. Taken together, our findings suggest that IL-18 could contribute to SLE pathogenesis through mediation of neutrophil dysfunction via the upregulation of IL18RAP expression.
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