RT Journal Article
SR Electronic
T1 22 Baricitinib inhibits B cell activation and ameliorates murine lupus
JF Lupus Science & Medicine
JO Lupus Sci & Med
FD Lupus Foundation of America
SP A17
OP A17
DO 10.1136/lupus-2019-lsm.22
VO 6
IS Suppl 1
A1 Lee, Jaeseon
A1 Jang, SeGwang
A1 Hong, Seung-Min
A1 Baek, SeungYe
A1 Park, Sung-Hwan
A1 Kwok, Seung-Ki
YR 2019
UL http://lupus.bmj.com/content/6/Suppl_1/A17.1.abstract
AB Background B cells carry out central roles in the pathogenesis of SLE by triggering tissue inflammation through autoreactive antibody-dependent responses. Baricitinib is a JAK1/2 inhibitor that blocks the downstream of multiple cytokine receptor signaling implicated in lupus pathogenesis.Methods We investigated the effect of Baricitinib to the differentiation of B cells in vitro. And female MRL/lpr mice were administered baricitinib (10 mg/kg) or vehicle (0.5% methyl cellulose) by gavage twice daily for 8 weeks, when determined serum levels of anti-ds DNA antibodies and pro-inflammatory cytokines (BAFF, IL-6 and IL-17), proteinuria, renal inflammation and IgG-C3 deposit. In vitro, Baricitinib suppressed the mRNA expression of AID, Bcl6, XBP-1, IRF4 and the production of IgG in B cells.Results In MRL/lpr model, Baricitinib-treated mice showed reduced levels of anti-dsDNA antibodies, proteinuria, and cytokines as compared with those of control mice. In addition, Baricitinib prevented renal pathology, as judged by changes in the histopathological scores of glomeruli with PAS stain and IgG-C3 deposition by confocal microscope. Finally, Baricitinib treatment significantly inhibited downstream of Jak/STAT signals in CD19 +B cells from spleen. In conclusion, this study revealed the regulatory effects of baricitinib on B cells and ameliorates murine lupus.Conclusions These results indicate that Jak inhibitors have the potential therapeutic approach for SLE.Funding Source(s): None