Authors:	Schlöder, Janine Berges, Carsten Lüssi, Felix Jonuleit, Helmut
Title:	Dimethyl fumarate therapy significantly improves the responsiveness of T cells in multiple sclerosis patients for immunoregulation by regulatory T cells
Online publication date:	17-Oct-2022
Year of first publication:	2017
Language:	english
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:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8060
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	International journal of molecular sciences 18 2
Pages or article number:	Art. 271
Publisher:	Molecular Diversity Preservation International
Publisher place:	Basel
Issue date:	2017
ISSN:	1422-0067 1661-6596
Publisher URL:	http://dx.doi.org/10.3390/ijms18020271
Publisher DOI:	10.3390/ijms18020271
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)