Autoren:	Schlöder, Janine Berges, Carsten Lüssi, Felix Jonuleit, Helmut
Titel:	Dimethyl fumarate therapy significantly improves the responsiveness of T cells in multiple sclerosis patients for immunoregulation by regulatory T cells
Online-Publikationsdatum:	17-Okt-2022
Erscheinungsdatum:	2017
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Multiple sclerosis (MS) is a chronic autoimmune disease caused by an insufficient suppression of autoreactive t lymphocytes. one reason for the lack of immunological control is the reduced responsiveness of t effector cells (teff) for the suppressive properties of regulatory t cells (treg), a process termed treg resistance. here we investigated whether the disease-modifying therapy of relapsing-remitting ms (rrms) with dimethyl fumarate (dmf) influences the sensitivity of t cells in the peripheral blood of patients towards treg-mediated suppression. we demonstrated that dmf restores responsiveness of teff to the suppressive function of treg in vitro, presumably by down-regulation of interleukin-6r (il-6r) expression on t cells. transfer of human immune cells into immunodeficient mice resulted in a lethal graft-versus-host reaction triggered by human cd4+ teff. this systemic inflammation can be prevented by activated treg after transfer of immune cells from dmf-treated ms patients, but not after injection of treg-resistant teff from therapy-naïve ms patients. furthermore, after dmf therapy, proliferation and expansion of t cells and the immigration into the spleen of the animals is reduced and modulated by activated treg. in summary, our data reveals that dmf therapy significantly improves the responsiveness of teff in ms patients to immunoregulation.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8060
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	International journal of molecular sciences 18 2
Seitenzahl oder Artikelnummer:	Art. 271
Verlag:	Molecular Diversity Preservation International
Verlagsort:	Basel
Erscheinungsdatum:	2017
ISSN:	1422-0067 1661-6596
URL der Originalveröffentlichung:	http://dx.doi.org/10.3390/ijms18020271
DOI der Originalveröffentlichung:	10.3390/ijms18020271
Enthalten in den Sammlungen:	DFG-OA-Publizieren (2012 - 2017)