T cell–specific STAT3 deficiency abrogates lupus nephritis. (October 2019)

• Record Type: Journal Article
• Authors: Yoshida, N; He, F; Kyttaris, V C
• Is Part Of: Lupus. Volume 28:Number 12(2019)
• Page Start: 1468
• Page End: 1472
• Publication Date: 2019-10
• Subjects: T cells -- STAT3 -- SLE -- murine lupus -- nephritis; Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1177/0961203319877242
• Languages: English
• ISSNs: 0961-2033

Abstract

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell–specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell–specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.