The Regulatory T-cell Transcription Factor Foxp3 Protects against Crescentic Glomerulonephritis

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 mem...

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Autores principales:	Chen Yang, Xiao-Ru Huang, Erik Fung, Hua-Feng Liu, Hui-Yao Lan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d92d7c3275e042558ab6ae9924f1e18b
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spelling	oai:doaj.org-article:d92d7c3275e042558ab6ae9924f1e18b2021-12-02T11:40:42ZThe Regulatory T-cell Transcription Factor Foxp3 Protects against Crescentic Glomerulonephritis10.1038/s41598-017-01515-82045-2322https://doaj.org/article/d92d7c3275e042558ab6ae9924f1e18b2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01515-8https://doaj.org/toc/2045-2322Abstract 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.Chen YangXiao-Ru HuangErik FungHua-Feng LiuHui-Yao LanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chen Yang Xiao-Ru Huang Erik Fung Hua-Feng Liu Hui-Yao Lan The Regulatory T-cell Transcription Factor Foxp3 Protects against Crescentic Glomerulonephritis
description	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.
format	article
author	Chen Yang Xiao-Ru Huang Erik Fung Hua-Feng Liu Hui-Yao Lan
author_facet	Chen Yang Xiao-Ru Huang Erik Fung Hua-Feng Liu Hui-Yao Lan
author_sort	Chen Yang
title	The Regulatory T-cell Transcription Factor Foxp3 Protects against Crescentic Glomerulonephritis
title_short	The Regulatory T-cell Transcription Factor Foxp3 Protects against Crescentic Glomerulonephritis
title_full	The Regulatory T-cell Transcription Factor Foxp3 Protects against Crescentic Glomerulonephritis
title_fullStr	The Regulatory T-cell Transcription Factor Foxp3 Protects against Crescentic Glomerulonephritis
title_full_unstemmed	The Regulatory T-cell Transcription Factor Foxp3 Protects against Crescentic Glomerulonephritis
title_sort	regulatory t-cell transcription factor foxp3 protects against crescentic glomerulonephritis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d92d7c3275e042558ab6ae9924f1e18b
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The Regulatory T-cell Transcription Factor Foxp3 Protects against Crescentic Glomerulonephritis

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