Up-regulation of the endoplasmic reticulum transmembrane protein UNC93B in the B cells of patients with active systemic lupus erythematosus
S Nakano, S Morimoto, S Suzuki, T Watanabe… - …, 2010 - academic.oup.com
S Nakano, S Morimoto, S Suzuki, T Watanabe, H Amano, Y Takasaki
Rheumatology, 2010•academic.oup.comObjectives. 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 …
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 …
Abstract
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.
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