Up-regulation of the endoplasmic reticulum transmembrane protein UNC93B in the B cells of patients with active systemic lupus erythematosus

作者：Nakano Souichiro^*; Morimoto Shinji; Suzuki Satoshi; Watanabe Takashi; Amano Hirofumi; Takasaki Yoshinari

来源：Rheumatology, 2010, 49(5): 876-881.

DOI：10.1093/rheumatology/keq001

• Systemic lupus erythematosus
• Innate immunity
• Toll-like receptor
• Toll-like receptor 7
• Toll-like receptor 9
• B cell
• UNC93B1
• Anti-dsDNA antibody
• Autoimmune disease
• Myeloid differentiation factor 88

Objectives. The transmembrane endoplasmic reticulum (ER) protein UNC93B plays an essential role in the normal response to signalling through intracellular Toll-like receptor (TLR) 3, TLR7, TLR8 and TLR9. In the current study, we examined the level of UNC93B expression on peripheral B cells from patients with active SLE, and investigated any correlation with SLE pathogenesis.
Methods. Peripheral blood mononuclear cells (PBMCs) and B cells from 43 active SLE patients were analysed by quantitative RT-PCR to determine the precise levels of UNC93B mRNA. We also analysed UNC93B protein expression on B cells from SLE patients using immunoblotting.
Results. The expression of UNC93B mRNA on PBMCs from active SLE patients was significantly higher than that of controls (P < 0.05). The intracellular expression level of UNC93B protein on CD20(+) B cells from active SLE patients was also higher than in the controls. Moreover, the expression of UNC93B on B cells from lupus patients correlated significantly with high titres of anti-dsDNA antibody (P < 0.05).
Conclusions. Up-regulation of the ER membrane protein UNC93B on human lupus B cells suggests that TLR9 and UNC93B play a partial role in the pathogenesis of SLE by inducing defective peripheral B-cell tolerance.

• 出版日期2010-5