FoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.

Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune...

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Autores principales:	Gerd Meyer zu Hörste, Steffen Cordes, Anne K Mausberg, Alla L Zozulya, Carsten Wessig, Tim Sparwasser, Christian Mathys, Heinz Wiendl, Hans-Peter Hartung, Bernd C Kieseier
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b681be4a42a48d7838886b895aa9a4b
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spelling	oai:doaj.org-article:8b681be4a42a48d7838886b895aa9a4b2021-11-25T05:57:49ZFoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.1932-620310.1371/journal.pone.0108756https://doaj.org/article/8b681be4a42a48d7838886b895aa9a4b2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108756https://doaj.org/toc/1932-6203Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies.Gerd Meyer zu HörsteSteffen CordesAnne K MausbergAlla L ZozulyaCarsten WessigTim SparwasserChristian MathysHeinz WiendlHans-Peter HartungBernd C KieseierPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e108756 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gerd Meyer zu Hörste Steffen Cordes Anne K Mausberg Alla L Zozulya Carsten Wessig Tim Sparwasser Christian Mathys Heinz Wiendl Hans-Peter Hartung Bernd C Kieseier FoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.
description	Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies.
format	article
author	Gerd Meyer zu Hörste Steffen Cordes Anne K Mausberg Alla L Zozulya Carsten Wessig Tim Sparwasser Christian Mathys Heinz Wiendl Hans-Peter Hartung Bernd C Kieseier
author_facet	Gerd Meyer zu Hörste Steffen Cordes Anne K Mausberg Alla L Zozulya Carsten Wessig Tim Sparwasser Christian Mathys Heinz Wiendl Hans-Peter Hartung Bernd C Kieseier
author_sort	Gerd Meyer zu Hörste
title	FoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.
title_short	FoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.
title_full	FoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.
title_fullStr	FoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.
title_full_unstemmed	FoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.
title_sort	foxp3+ regulatory t cells determine disease severity in rodent models of inflammatory neuropathies.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8b681be4a42a48d7838886b895aa9a4b
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FoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.

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