Pathological conversion of regulatory T cells is associated with loss of allotolerance

Abstract CD4+CD25+Foxp3+ Regulatory T cells (Tregs) play a critical role in immune tolerance. The plasticity and functional adaptability of Tregs in an inflammatory microenvironment has been demonstrated in autoimmunity. Here, using a double transgenic mouse model that permits Foxp3 lineage tracing,...

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Autores principales:	Jing Hua, Takenori Inomata, Yihe Chen, William Foulsham, William Stevenson, Tina Shiang, Jeffrey A. Bluestone, Reza Dana
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e0acee4685d7438c894e55fd71ae9255
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spelling	oai:doaj.org-article:e0acee4685d7438c894e55fd71ae92552021-12-02T16:08:13ZPathological conversion of regulatory T cells is associated with loss of allotolerance10.1038/s41598-018-25384-x2045-2322https://doaj.org/article/e0acee4685d7438c894e55fd71ae92552018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25384-xhttps://doaj.org/toc/2045-2322Abstract CD4+CD25+Foxp3+ Regulatory T cells (Tregs) play a critical role in immune tolerance. The plasticity and functional adaptability of Tregs in an inflammatory microenvironment has been demonstrated in autoimmunity. Here, using a double transgenic mouse model that permits Foxp3 lineage tracing, we investigated the phenotypic plasticity of Foxp3+ Tregs in a well-characterized murine model of corneal transplantation. In order to subvert the normal immune privilege of the cornea and foster an inflammatory milieu, host mice were exposed to desiccating stress prior to transplantation. Treg frequencies and function were decreased following desiccating stress, and this corresponded to decreased graft survival. A fraction of Tregs converted to IL-17+ or IFNγ+ ‘exFoxp3’ T cells that were phenotypically indistinguishable from effector Th17 or Th1 cells, respectively. We investigated how Foxp3 expression is modulated in different Treg subsets, demonstrating that neuropilin-1− peripherally-derived Tregs are particularly susceptible to conversion to IL-17+/IFNγ+ exFoxp3 cells in response to cues from their microenvironment. Finally, we show that IL-6 and IL-23 are implicated in the conversion of Tregs to exFoxp3 cells. This report demonstrates that the pathological conversion of Tregs contributes to the loss of corneal immune privilege.Jing HuaTakenori InomataYihe ChenWilliam FoulshamWilliam StevensonTina ShiangJeffrey A. BluestoneReza DanaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing Hua Takenori Inomata Yihe Chen William Foulsham William Stevenson Tina Shiang Jeffrey A. Bluestone Reza Dana Pathological conversion of regulatory T cells is associated with loss of allotolerance
description	Abstract CD4+CD25+Foxp3+ Regulatory T cells (Tregs) play a critical role in immune tolerance. The plasticity and functional adaptability of Tregs in an inflammatory microenvironment has been demonstrated in autoimmunity. Here, using a double transgenic mouse model that permits Foxp3 lineage tracing, we investigated the phenotypic plasticity of Foxp3+ Tregs in a well-characterized murine model of corneal transplantation. In order to subvert the normal immune privilege of the cornea and foster an inflammatory milieu, host mice were exposed to desiccating stress prior to transplantation. Treg frequencies and function were decreased following desiccating stress, and this corresponded to decreased graft survival. A fraction of Tregs converted to IL-17+ or IFNγ+ ‘exFoxp3’ T cells that were phenotypically indistinguishable from effector Th17 or Th1 cells, respectively. We investigated how Foxp3 expression is modulated in different Treg subsets, demonstrating that neuropilin-1− peripherally-derived Tregs are particularly susceptible to conversion to IL-17+/IFNγ+ exFoxp3 cells in response to cues from their microenvironment. Finally, we show that IL-6 and IL-23 are implicated in the conversion of Tregs to exFoxp3 cells. This report demonstrates that the pathological conversion of Tregs contributes to the loss of corneal immune privilege.
format	article
author	Jing Hua Takenori Inomata Yihe Chen William Foulsham William Stevenson Tina Shiang Jeffrey A. Bluestone Reza Dana
author_facet	Jing Hua Takenori Inomata Yihe Chen William Foulsham William Stevenson Tina Shiang Jeffrey A. Bluestone Reza Dana
author_sort	Jing Hua
title	Pathological conversion of regulatory T cells is associated with loss of allotolerance
title_short	Pathological conversion of regulatory T cells is associated with loss of allotolerance
title_full	Pathological conversion of regulatory T cells is associated with loss of allotolerance
title_fullStr	Pathological conversion of regulatory T cells is associated with loss of allotolerance
title_full_unstemmed	Pathological conversion of regulatory T cells is associated with loss of allotolerance
title_sort	pathological conversion of regulatory t cells is associated with loss of allotolerance
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/e0acee4685d7438c894e55fd71ae9255
work_keys_str_mv	AT jinghua pathologicalconversionofregulatorytcellsisassociatedwithlossofallotolerance AT takenoriinomata pathologicalconversionofregulatorytcellsisassociatedwithlossofallotolerance AT yihechen pathologicalconversionofregulatorytcellsisassociatedwithlossofallotolerance AT williamfoulsham pathologicalconversionofregulatorytcellsisassociatedwithlossofallotolerance AT williamstevenson pathologicalconversionofregulatorytcellsisassociatedwithlossofallotolerance AT tinashiang pathologicalconversionofregulatorytcellsisassociatedwithlossofallotolerance AT jeffreyabluestone pathologicalconversionofregulatorytcellsisassociatedwithlossofallotolerance AT rezadana pathologicalconversionofregulatorytcellsisassociatedwithlossofallotolerance
_version_	1718384565043593216

Pathological conversion of regulatory T cells is associated with loss of allotolerance

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