Abstract |
Regulatory T cells (Tregs) have been shown to play a protective role in glomerulonephritis (GN) and Foxp3 is a master transcription factor in Treg development. In this study, we examined the functional role and mechanisms of Foxp3 in a mouse model of accelerated anti-glomerular basement membrane ( anti-GBM) GN induced in antigen-primed Foxp3 transgenic (Tg) mice. Compared with littermate of wildtype (WT) mice in which induced severe crescentic GN developed with progressive renal dysfunction, Foxp3 Tg mice had reduced crescent formation, urinary protein excretion, plasma creatinine and decline in creatinine clearance. The protective role of Foxp3 in crescentic GN was associated with a markedly suppressed expression of proinflammatory interleukin-1 beta (IL-1β), tumour necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1), and diminished infiltration of the kidneys by CD3+ T cells and F4/80+ macrophages. Moreover, overexpression of Foxp3 resulted in a significant increase in CD4+ Foxp3+ Tregs systemically and in the diseased kidneys, thereby blunting Th1, Th2, and Th17 responses systemically and in the kidneys. In conclusion, Foxp3 protects against kidney injury in crescentic GN through enhancement of Treg numbers and function, and suppression of Th1, Th2 and Th17 immune responses at the systemic and local tissue levels.
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Authors | Chen Yang, Xiao-Ru Huang, Erik Fung, Hua-Feng Liu, Hui-Yao Lan |
Journal | Scientific reports
(Sci Rep)
Vol. 7
Issue 1
Pg. 1481
(05 03 2017)
ISSN: 2045-2322 [Electronic] England |
PMID | 28469165
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Differentiation
- Ccl2 protein, mouse
- Chemokine CCL2
- Forkhead Transcription Factors
- Foxp3 protein, mouse
- IL1B protein, mouse
- Interleukin-1beta
- Tumor Necrosis Factor-alpha
- monocyte-macrophage differentiation antigen
- Creatinine
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Topics |
- Animals
- Antigens, Differentiation
(genetics, immunology)
- Cell Movement
- Chemokine CCL2
(genetics, immunology)
- Creatinine
(blood)
- Forkhead Transcription Factors
(genetics, immunology)
- Gene Expression Regulation
- Glomerulonephritis
(genetics, immunology, pathology, prevention & control)
- Interleukin-1beta
(genetics, immunology)
- Kidney Glomerulus
(immunology, pathology)
- Macrophages
(immunology, pathology)
- Mice
- Mice, Transgenic
- Proteinuria
(genetics, immunology, pathology, prevention & control)
- Signal Transduction
- T-Lymphocytes, Helper-Inducer
(immunology, pathology)
- T-Lymphocytes, Regulatory
(immunology, pathology)
- Tumor Necrosis Factor-alpha
(genetics, immunology)
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