Elevated Interleukin-18 Receptor Accessory Protein Mediates Enhancement in Reactive Oxygen Species Production in Neutrophils of Systemic Lupus Erythematosus Patients.

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.

MicroRNA-mediated immune regulation in rheumatic diseases.

MicroRNAs (miRNAs) are endogenous small, non-coding RNAs that regulate genome expression at the post-transcriptional level. They are involved in a wide range of physiological processes including the maintenance of immune homeostasis and normal function. Accumulating evidence from animal studies show that alterations in pan or specific miRNA expression would break immunological tolerance, leading to autoimmunity. Differential miRNA expressions have also been documented in patients of many autoimmune disorders. In this review, we highlight the evidence that signifies the critical role of miRNAs in autoimmunity, specifically on their regulatory roles in the pathogenesis of several rheumatic diseases including systemic lupus erythematosus, rheumatoid arthritis and spondyloarthritis. The potential of miRNAs as biomarkers and therapeutic targets is also discussed. Manipulation of dysregulated miRNAs in vivo through miRNA delivery or inhibition offers promise for new therapeutic strategies in treating rheumatic diseases.