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Signal Transducer and Activator of Transcription (STAT) 3 Inhibition Delays The Onset Of Lupus Nephritis In MRL/lpr Mice #MMPMID25869298
Edwards LJ; Mizui M; Kyttaris V
Clin Immunol 2015[Jun]; 158 (2): 221-30 PMID25869298show ga
The transcription factor STAT3 is overexpressed and hyperactivated in T cells from SLE patients. STAT3 plays a central role in T cell differentiation into Th17 and T follicular helper cells, two subsets that orchestrate autoimmune responses in SLE. Moreover, STAT3 is important in chemokine-mediated T cell migration. To better understand its role in SLE, we inhibited STAT3 in lupus-prone mice using the small molecule Stattic. Stattic-treated mice exhibited delayed onset of proteinuria (3 weeks later than controls), and had lower levels of anti-dsDNA antibodies and inflammatory cytokines. Inhibitor treatment reduced lymphadenopathy, resulted in a 3-fold decrease in total T cell number, and a 4-fold decrease in the numbers of T follicular helper cells. In vitro experiments showed that Stattic-treated T cells exhibited decreased proliferation and a decrease in ability to migrate to CXCL12. We propose that STAT3 inhibition represents a therapeutic target in SLE, particularly lupus nephritis.