The expression of XBP1s in B lymphocytes is critical for pristane-induced lupusnephritis in mice.

In this study, we systematically evaluated the changes in B cell activation induced by the Xbp1 splicing inhibitor STF083010 in a pristane-induced lupus mouse model. The lupus mouse model was successfully established, as indicated by the presence of LN with markedly increased urine protein levels, renal deposition of Ig and mesangial cell proliferation. In lupus mice, B cell hyperactivity was confirmed by increased CD40 and B cell activating factor (BAFF) levels. B cell activation and plasma cell overproduction were determined by increases in CD40+ and CD138+ cells in the spleens of lupus mice by flow cytometry and further confirmed by CD45R and Ig light chain staining in the splenic tissues of lupus mice. The mRNA and protein expression of XBP1s in B cells was assessed by real-time PCR, western blotting, and immunofluorescence analysis and were increased in lupus mice. In addition, almost all changes were reversed by STF083010 treatment. However, the expression of XBP1s in kidneys did not change when the mice were exposed to pristane and STF083010. Taken together, these findings suggest that the expression of XBP1s in B cells plays key roles in SLE and LN development. Blocking the XBP1s pathway may be a potential strategy for SLE and LN treatment. PMID: 32249615 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research