title: FoxP3+ regulatory T cells determine disease severity in rodent models of inflammatory neuropathies.
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.
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Meyer zu Hörste
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Cordes
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Mausberg
authors.affiliation: Department of Neurology, Julius-Maximilians-University, Würzburg, Germany.
authors.forename: Alla L
authors.initials: AL
authors.lastname: Zozulya
authors.affiliation: Department of Neurology, Julius-Maximilians-University, Würzburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Wessig
authors.affiliation: Institute for Infection Immunology, TWINCORE, Center for Experimental and Clinical Infection Research, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Department of Diagnostic and Interventional Radiology, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mathys
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany.
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008212:Lymphocyte Depletion; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009186:Myelin Sheath / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D017933:Peripheral Nervous System / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000906:Antibodies; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D053645:Interleukin-2 Receptor alpha Subunit