FoxP3+ Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies.

2.50
Hdl Handle:
http://hdl.handle.net/10033/334481
Title:
FoxP3+ Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies.
Authors:
Meyer Zu Hörste, Gerd; Cordes, Steffen; Mausberg, Anne K; Zozulya, Alla L; Wessig, Carsten; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Mathys, Christian; Wiendl, Heinz; Hartung, Hans-Peter; Kieseier, Bernd C
Abstract:
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.
Affiliation:
Department of Neurology, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany.
Citation:
FoxP3+ Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies. 2014, 9 (10):e108756 PLoS ONE
Journal:
PloS one
Issue Date:
2014
URI:
http://hdl.handle.net/10033/334481
DOI:
10.1371/journal.pone.0108756
PubMed ID:
25286182
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorMeyer Zu Hörste, Gerden
dc.contributor.authorCordes, Steffenen
dc.contributor.authorMausberg, Anne Ken
dc.contributor.authorZozulya, Alla Len
dc.contributor.authorWessig, Carstenen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorMathys, Christianen
dc.contributor.authorWiendl, Heinzen
dc.contributor.authorHartung, Hans-Peteren
dc.contributor.authorKieseier, Bernd Cen
dc.date.accessioned2014-11-11T13:10:24Zen
dc.date.available2014-11-11T13:10:24Zen
dc.date.issued2014en
dc.identifier.citationFoxP3+ Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies. 2014, 9 (10):e108756 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid25286182en
dc.identifier.doi10.1371/journal.pone.0108756en
dc.identifier.urihttp://hdl.handle.net/10033/334481en
dc.description.abstractInflammatory 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.en
dc.language.isoenen
dc.titleFoxP3+ Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies.en
dc.typeArticleen
dc.contributor.departmentDepartment of Neurology, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany.en
dc.identifier.journalPloS oneen

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