Dopaminergic stimulation leads B-cell infiltration into the central nervous system upon autoimmunity

Simple item page
dc.article.number292
dc.contributor.authorPrado, Carolina
dc.contributor.authorOsorio Barrios, Francisco
dc.contributor.authorFalcón, Paulina
dc.contributor.authorEspinoza, Alexandra
dc.contributor.authorSaez, Juan José
dc.contributor.authorYuseff Sepúlveda, María Isabel
dc.contributor.authorPacheco, Rodrigo
dc.date.accessioned2021-12-22T16:24:07Z
dc.date.available2021-12-22T16:24:07Z
dc.date.issued2021
dc.date.updated2021-12-19T01:03:12Z
dc.description.abstractAbstract Background Recent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation of immune cells plays an important role in the physiopathology of inflammatory disorders. Multiple sclerosis (MS) is an inflammatory disease involving a CD4+ T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models has suggested that B cells play a fundamental role as antigen-presenting cells (APC) re-stimulating CD4+ T cells in the CNS as well as regulating T-cell response by mean of inflammatory or anti-inflammatory cytokines. Here, we addressed the role of the dopamine receptor D3 (DRD3), which displays the highest affinity for dopamine, in B cells in animal models of MS. Methods Mice harbouring Drd3-deficient or Drd3-sufficient B cells were generated by bone marrow transplantation into recipient mice devoid of B cells. In these mice, we compared the development of experimental autoimmune encephalomyelitis (EAE) induced by immunization with a myelin oligodendrocyte glycoprotein (MOG)-derived peptide (pMOG), a model that leads to CNS-autoimmunity irrespective of the APC-function of B cells, or by immunization with full-length human MOG protein (huMOG), a model in which antigen-specific activated B cells display a fundamental APC-function in the CNS. APC-function was assessed in vitro by pulsing B cells with huMOG-coated beads and then co-culturing with MOG-specific T cells. Results Our data show that the selective Drd3 deficiency in B cells abolishes the disease development in the huMOG-induced EAE model. Mechanistic analysis indicates that although DRD3-signalling did not affect the APC-function of B cells, DRD3 favours the CNS-tropism in a subset of pro-inflammatory B cells in the huMOG-induced EAE model, an effect that was associated with higher CXCR3 expression. Conversely, the results show that the selective Drd3 deficiency in B cells exacerbates the disease severity in the pMOG-induced EAE model. Further analysis shows that DRD3-stimulation increased the expression of the CNS-homing molecule CD49d in a B-cell subset with anti-inflammatory features, thus attenuating EAE manifestation in the pMOG-induced EAE model. Conclusions Our findings demonstrate that DRD3 in B cells exerts a dual role in CNS-autoimmunity, favouring CNS-tropism of pro-inflammatory B cells with APC-function and promoting CNS-homing of B cells with anti-inflammatory features. Thus, these results show DRD3-signalling in B cells as a critical regulator of CNS-autoimmunity.
dc.format.extent20 páginas
dc.fuente.origenAutoarchivo
dc.identifier.citationJournal of Neuroinflammation. 2021 Dec 17;18(1):292
dc.identifier.doi10.1186/s12974-021-02338-1
dc.identifier.urihttps://doi.org/10.1186/s12974-021-02338-1
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/63078
dc.identifier.wosidWOS:000731271400004
dc.information.autorucFacultad de Ciencias Biológicas ; Yuseff Sepúlveda, María Isabel ; 0000-0001-8172-3785 ; 12456311
dc.issue.numeroNo. 1
dc.language.isoen
dc.nota.accesoContenido completo
dc.revistaJournal of Neuroinflammationes_ES
dc.rightsacceso abierto
dc.subjectRegulatory B lymphocyteses_ES
dc.subjectAntigen-presenting cellses_ES
dc.subjectChemokine receptorses_ES
dc.subjectNeuroinfammationes_ES
dc.subjectExperimental autoimmune encephalomyelitises_ES
dc.subjectCentral nervous system hominges_ES
dc.subject.ddc570
dc.subject.deweyBiologíaes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.subject.otherLinfocitos Bes_ES
dc.subject.otherCélulas con antígeno presente - Inmunologíaes_ES
dc.titleDopaminergic stimulation leads B-cell infiltration into the central nervous system upon autoimmunity
dc.typeartículo
sipa.codpersvinculados12456311
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
12974_2021_Article_2338.pdf
Size:
2.31 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
0 B
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Artículos de revistas