Twist1 in T Lymphocytes Augments Kidney Fibrosis after Ureteral Obstruction.
BACKGROUND: Twist1 is a basic helix-loop-helix domain-containing transcription factor that participates in diverse cellular functions, including epithelial-mesenchymal transition and the cellular immune response. Although Twist1 plays critical roles in the initiation and progression of kidney diseases, the effects of Twist1 in the T lymphocyte on the progression of renal fibrosis require elucidation. METHODS: 129/SvEv mice with a floxed allele for the gene encoding Twist1 or TNFα were bred with CD4-Cre mice to yield CD4-Cre+ Twist1flox/flox (Twist1-TKO) or CD4-Cre+ TNFflox/flox (TNF-TKO) mice with robust, but selective, deletion of Twist1 or TNFα mRNA in T cells, respectively. Twist1 TKO, TNF TKO, and WT controls underwent UUO with assessment of kidney fibrosis and T-cell phenotype at 14 days. RESULTS: Compared with WT controls, obstructed kidneys from Twist1 TKO mice had attenuated extracellular matrix deposition. Despite this diminished fibrosis, Twist1 TKO obstructed kidneys contained more CD8+ T cells than in WTs. These intrarenal CD8+ T cells exhibited greater activation and higher levels of TNFα expression than those from WT obstructed kidneys. Further, we found that selective deletion of TNFα from T cells exaggerated renal scar formation and injury after UUO, highlighting the capacity of T-cell TNF to constrain fibrosis in the kidney. CONCLUSIONS: Twist1 in T cells promotes kidney fibrogenesis, in part, by curtailing the renal accumulation of TNF-elaborating T cells.
Duke Scholars
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Related Subject Headings
- Ureteral Obstruction
- Twist-Related Protein 1
- Mice, Knockout
- Mice
- Kidney Diseases
- Kidney
- Fibrosis
- Disease Models, Animal
- CD8-Positive T-Lymphocytes
- Animals
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Ureteral Obstruction
- Twist-Related Protein 1
- Mice, Knockout
- Mice
- Kidney Diseases
- Kidney
- Fibrosis
- Disease Models, Animal
- CD8-Positive T-Lymphocytes
- Animals