dc.contributor.author |
Derdelinckx, Judith |
dc.contributor.author |
Mansilla Lopez, Maria Jose |
dc.contributor.author |
De Laere, Maxime |
dc.contributor.author |
Lee, Wai-Ping |
dc.contributor.author |
Navarro-Barriuso, Juan |
dc.contributor.author |
Wens, Inez |
dc.contributor.author |
Nkansah, Irene |
dc.contributor.author |
Daans, Jasmijn |
dc.contributor.author |
De Reu, Hans |
dc.contributor.author |
Jolanta Keliris, Aneta |
dc.contributor.author |
Van Audekerke, Johan |
dc.contributor.author |
Vanreusel, Verdi |
dc.contributor.author |
Pieters, Zoë |
dc.contributor.author |
Van Der Linden, Annemie |
dc.contributor.author |
Verhoye, Maraleen |
dc.contributor.author |
Molenberghs, Geert |
dc.contributor.author |
Hens, Niel |
dc.contributor.author |
Goossens, Herman |
dc.contributor.author |
Willekens, Barbara |
dc.contributor.author |
Cras, Patrick |
dc.contributor.author |
Ponsaerts, Peter |
dc.contributor.author |
Berneman, Zwi |
dc.contributor.author |
Martínez Cáceres, Eva María |
dc.contributor.author |
Cools, Nathalie |
dc.date |
2019 |
dc.identifier |
https://ddd.uab.cat/record/223975 |
dc.identifier |
urn:10.1186/s12974-019-1541-1 |
dc.identifier |
urn:oai:ddd.uab.cat:223975 |
dc.identifier |
urn:scopus_id:85071071610 |
dc.identifier |
urn:articleid:17422094v16n1p167 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/3395dadc-c359-4162-87ce-9be446fdd800 |
dc.identifier |
urn:pmid:31416452 |
dc.identifier |
urn:pmc-uid:6696692 |
dc.identifier |
urn:pmcid:PMC6696692 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:6696692 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Journal of neuroinflammation ; Vol. 16 (August 2019), art. 167 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
dc.subject |
Messenger RNA electroporation |
dc.subject |
Tolerogenic dendritic cells |
dc.subject |
Antigen-specific treatment |
dc.subject |
Experimental autoimmune encephalomyelitis |
dc.subject |
Multiple sclerosis |
dc.subject |
Tolerance induction |
dc.title |
Clinical and immunological control of experimental autoimmune encephalomyelitis by tolerogenic dendritic cells loaded with MOG-encoding mRNA |
dc.type |
Article |
dc.description.abstract |
Background: Although effective in reducing relapse rate and delaying progression, current therapies for multiple sclerosis (MS) do not completely halt disease progression. T cell autoimmunity to myelin antigens is considered one of the main mechanisms driving MS. It is characterized by autoreactivity to disease-initiating myelin antigen epitope(s), followed by a cascade of epitope spreading, which are both strongly patient-dependent. Targeting a variety of MS-associated antigens by myelin antigen-presenting tolerogenic dendritic cells (tolDC) is a promising treatment strategy to re-establish tolerance in MS. Electroporation with mRNA encoding myelin proteins is an innovative technique to load tolDC with the full spectrum of naturally processed myelin-derived epitopes. Methods: In this study, we generated murine tolDC presenting myelin oligodendrocyte glycoprotein (MOG) using mRNA electroporation and we assessed the efficacy of MOG mRNA-electroporated tolDC to dampen pathogenic T cell responses in experimental autoimmune encephalomyelitis (EAE). For this, MOG-immunized C57BL/6 mice were injected intravenously at days 13, 17, and 21 post-disease induction with 1α,25-dihydroxyvitamin D-treated tolDC electroporated with MOG-encoding mRNA. Mice were scored daily for signs of paralysis. At day 25, myelin reactivity was evaluated following restimulation of splenocytes with myelin-derived epitopes. Ex vivo magnetic resonance imaging (MRI) was performed to assess spinal cord inflammatory lesion load. Results: Treatment of MOG-immunized C57BL/6 mice with MOG mRNA-electroporated or MOG-pulsed tolDC led to a stabilization of the EAE clinical score from the first administration onwards, whereas it worsened in mice treated with non-antigen-loaded tolDC or with vehicle only. In addition, MOG-specific pro-inflammatory pathogenic T cell responses and myelin antigen epitope spreading were inhibited in the peripheral immune system of tolDC-treated mice. Finally, magnetic resonance imaging analysis of hyperintense spots along the spinal cord was in line with the clinical score. Conclusions: Electroporation with mRNA is an efficient and versatile tool to generate myelin-presenting tolDC that are capable to stabilize the clinical score in EAE. These results pave the way for further research into mRNA-electroporated tolDC treatment as a patient-tailored therapy for MS. |