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Signal transducer and activator of transcription (STAT) 3 inhibition delays the onset of lupus nephritis in MRL/lpr mice.
- Source :
-
Clinical immunology (Orlando, Fla.) [Clin Immunol] 2015 Jun; Vol. 158 (2), pp. 221-30. Date of Electronic Publication: 2015 Apr 11. - Publication Year :
- 2015
-
Abstract
- 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.<br /> (Copyright © 2015. Published by Elsevier Inc.)
- Subjects :
- Animals
Cyclic S-Oxides pharmacology
Cytokines genetics
Cytokines metabolism
Immunoglobulin G metabolism
Inflammation metabolism
Kidney metabolism
Kidney pathology
Lupus Nephritis metabolism
Mice
Mice, Inbred MRL lpr
STAT3 Transcription Factor genetics
STAT3 Transcription Factor metabolism
T-Lymphocytes metabolism
Gene Expression Regulation drug effects
Lupus Nephritis pathology
STAT3 Transcription Factor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1521-7035
- Volume :
- 158
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical immunology (Orlando, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 25869298
- Full Text :
- https://doi.org/10.1016/j.clim.2015.04.004