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T cell–specific STAT3 deficiency abrogates lupus nephritis
- Source :
- Lupus
- Publication Year :
- 2019
- Publisher :
- SAGE Publications, 2019.
-
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.
- Subjects :
- STAT3 Transcription Factor
0301 basic medicine
Chemokine
T-Lymphocytes
T cell
Lupus nephritis
Article
Mice
03 medical and health sciences
0302 clinical medicine
Rheumatology
medicine
Animals
Humans
Lupus Erythematosus, Systemic
skin and connective tissue diseases
STAT3
B cell
Autoantibodies
Mice, Knockout
biology
business.industry
Glomerulonephritis
medicine.disease
Lupus Nephritis
Cyclic S-Oxides
030104 developmental biology
medicine.anatomical_structure
biology.protein
Cancer research
Cytokines
Chemokines
Antibody
business
Nephritis
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14770962 and 09612033
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Lupus
- Accession number :
- edsair.doi.dedup.....49a5542b3acead0ec24a0cb41a9b2121