Expression profiles of toll-like receptor signaling pathway related genes in microscopic polyangiitis in Chinese people

Recent, emerging evidence indicates that inappropriate regulation of toll-like receptor (TLR) signaling pathway plays a fundamental role in the development of autoimmune diseases including microscopic polyangiitis (MPA). However, the role of TLR-related cytokines in microscopic polyangiitis remains unclear. To further investigate the role and imbalance of TLR-related cytokines in the pathogenesis of MPA, a quantitative reverse transcription polymerase chain reaction (RT-PCR) array (Human TLR for Autoimmunity & Inflammation PCR Array) analysis was performed to study TLR-related gene expression in peripheral blood mononuclear cells (PBMC) of 10 new-onset patients with MPA and 10 healthy volunteers. We then used quantitative real-time PCR to validate the array test. When gene expression for 84 target genes related to the TLR pathway in MPA patients was compared to the mean of normal controls, 13 genes (BCL3, CD14, CXCL11, CXCL9, FADD, IL10, IRAK3, IRF7, MUC1, TLR1, TLR4, TLR6, TOLLIP) were up-regulated and 10 genes (ATF3, CHUK, CIITA, CXCL10, IFNA7, JUN, RIPK2, SARM1, SOCS1, TLR10) were down-regulated. These genes encompassed a diverse group of proteins including toll-like receptors, negative regulation molecules, adaptors and TLR interacting proteins, effectors, downstream pathway and target genes, activating transcription factors and inflammatory cytokines. In conclusion, the expression profile of PBMCs in this study suggests that the TLR signaling pathway may be involved in the pathogenesis of MPA. This finding may provide new insights in understanding the pathogenesis of MPA as well as provide new therapeutic targets.