Therapeutic role of interferon-γ in experimental autoimmune encephalomyelitis is mediated through a tolerogenic subset of splenic CD11b+ myeloid cells

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dc.article.number144
dc.catalogadoryvc
dc.contributor.authorArellano, Gabriel
dc.contributor.authorAcuña, Eric
dc.contributor.authorLoda, Eileah
dc.contributor.authorMoore, Lindsay
dc.contributor.authorTichauer Calderón, Juan Enrique
dc.contributor.authorCastillo, Cristian
dc.contributor.authorVergara, Fabian
dc.contributor.authorBurgos Cañete, Paula Isabel
dc.contributor.authorPeñaloza-MacMaster, Pablo
dc.contributor.authorMiller, Stephen D.
dc.contributor.authorNaves, Rodrigo
dc.date.accessioned2024-06-06T14:07:55Z
dc.date.available2024-06-06T14:07:55Z
dc.date.issued2024
dc.description.abstractCumulative evidence has established that Interferon (IFN)-γ has both pathogenic and protective roles in Multiple Sclerosis and the animal model, Experimental Autoimmune Encephalomyelitis (EAE). However, the underlying mechanisms to the beneficial effects of IFN-γ are not well understood. In this study, we found that IFN-γ exerts therapeutic effects on chronic, relapsing-remitting, and chronic progressive EAE models. The frequency of regulatory T (Treg) cells in spinal cords from chronic EAE mice treated with IFN-γ was significantly increased with no effect on Th1 and Th17 cells. Consistently, depletion of FOXP3-expressing cells blocked the protective effects of IFN-γ, indicating that the therapeutic effect of IFN-γ depends on the presence of Treg cells. However, IFN-γ did not trigger direct in vitro differentiation of Treg cells. In vivo administration of blocking antibodies against either interleukin (IL)-10, transforming growth factor (TGF)-β or program death (PD)-1, revealed that the protective effects of IFN-γ in EAE were also dependent on TGF-β and PD-1, but not on IL-10, suggesting that IFN-γ might have an indirect role on Treg cells acting through antigen-presenting cells. Indeed, IFN-γ treatment increased the frequency of a subset of splenic CD11b+ myeloid cells expressing TGF-β-Latency Associated Peptide (LAP) and program death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)-1-dependent manner. Furthermore, splenic CD11b+ cells from EAE mice preconditioned in vitro with IFN-γ and myelin oligodendrocyte glycoprotein (MOG) peptide exhibited a tolerogenic phenotype with the capability to induce conversion of naïve CD4+ T cells mediated by secretion of TGF-β. Remarkably, adoptive transfer of splenic CD11b+ cells from IFN-γ-treated EAE mice into untreated recipient mice ameliorated clinical symptoms of EAE and limited central nervous system infiltration of mononuclear cells and effector helper T cells. These results reveal a novel cellular and molecular mechanism
dc.fechaingreso.objetodigital2024-06-06
dc.fuente.origenBiomed Central
dc.identifier.doi10.1186/s12974-024-03126-3
dc.identifier.urihttps://doi.org/10.1186/s12974-024-03126-3
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86494
dc.information.autorucEscuela de Medicina;Burgos Cañete, Paula Isabel;0000-0002-1526-0126;93093
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaJournal of Neuroinflammation
dc.rightsacceso abierto
dc.rights.licenseCC0 1.0 Universal
dc.rights.urihttps://creativecommons.org/publicdomain/zero/1.0/
dc.subjectMultiple sclerosis
dc.subjectExperimental autoimmune encephalomyelitis
dc.subjectInterferon-γ
dc.subjectRegulatory T cells
dc.subjectCD11b+ cells
dc.subjectTGF-β
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleTherapeutic role of interferon-γ in experimental autoimmune encephalomyelitis is mediated through a tolerogenic subset of splenic CD11b+ myeloid cells
dc.typeartículo
dc.volumen21
sipa.codpersvinculados93093
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