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Dissecting the role of microRNAs in effector versus regulatory CD4+ T cell differentiation during (auto)immune responses in vivo

2023-11Conference object Open access
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dc.contributor.authorCunha, Carolina
dc.contributor.authorRomero, Paula Vargas
dc.contributor.authorInácio, Daniel
dc.contributor.authorPais, Ana Teresa
dc.contributor.authorPelicano, Catarina
dc.contributor.authorSobral, Daniel
dc.contributor.authorCosta, Marina
dc.contributor.authorMensurado, Sofia
dc.contributor.authorSousa, Natacha Gonçalves
dc.contributor.authorPapotto, Pedro
dc.contributor.authorEnguita, Francisco
dc.contributor.authorGomes, Anita Q.
dc.contributor.authorSilva-Santos, Bruno
dc.date.accessioned2024-01-15T14:35:40Z
dc.date.available2024-01-15T14:35:40Z
dc.date.issued2023-11
dc.description.abstractIntroduction: MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They have been implicated in the regulation of the differentiation and function of CD4+ T cell subsets, key players in host defense against pathogens, but also responsible for immune-mediated diseases depending on the correct vs incorrect balance, respectively, between pro-inflammatory effector CD4+T cells, including the IFN-γ-producers T helper 1 (Th)1 and the IL-17-producers Th17 cells, and anti-inflammatory regulatory T cells (Treg). While individual miRNAs were found to regulate the differentiation of specific CD4+ T cell populations, an approach based on in vivo responses is still missing and is key to understanding how miRNA networks control this balance in pathophysiology. Methodology: We have established a triple reporter mouse for Ifng, Il17, and Foxp3, and subjected it to experimental autoimmune encephalomyelitis (EAE). We performed miRNA-seq analysis on Th1, Th17, and Treg cells isolated from the spleen and lymph nodes (LNs) at the peak plateau stage to identify miRNA candidates specifically expressed in one of the cell populations. We have in vivo modulated their expression levels using antagomiRs observed the course of EAE progression and characterised their upstream regulation in vitro in either Th1 or Th17 differentiation conditions. Results: The miRNA-seq data has allowed the identification of 110 miRNAs differentially expressed between effector (Th1 and Th17) and regulatory (Treg) subsets. From those, 9 were specifically upregulated in one population versus the others. In vivo miRNA modulation showed that silencing miR-122 precipitated the onset of EAE, whereas overexpressing miR-1247 decreased the severity of the disease. Cytokine-regulated miR-1247 and miR-122 expression levels are inversely associated with pathogenic signatures of Th1 and Th17 cells between lymphoid and central nervous systems. Discussion: Our results suggest that miR-122 and miR-1247 act as peripheral brakes to CD4+ T cell pathogenicity that are overruled in the inflamed target organ. These findings may have important implications for autoimmune diseases.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCunha C, Romero PV, Inácio D, Pais AT, Pelicano C, Gomes AQ, et al. Dissecting the role of microRNAs in effector versus regulatory CD4+ T cell differentiation during (auto)immune responses in vivo. In: 27th Annual meeting of the Portuguese Society of Human Genetics, Instituto Superior Técnico, November 23-25, 2023. Medicine. 2025;104(4):e39478.pt_PT
dc.identifier.doi10.1097/MD.0000000000039478
dc.identifier.urihttp://hdl.handle.net/10400.21/16886
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relation.publisherversionhttps://www.spp.pt/eventos/default.asp?ida=12618&ID=136pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectMicroRNApt_PT
dc.subjectCD4+ T cellpt_PT
dc.titleDissecting the role of microRNAs in effector versus regulatory CD4+ T cell differentiation during (auto)immune responses in vivopt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceLisboapt_PT
person.familyNameGomes
person.givenNameAnita
person.identifier.ciencia-id4B10-E015-52B7
person.identifier.orcid0000-0002-3348-0448
person.identifier.ridC-3580-2014
person.identifier.scopus-author-id7202386033
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isAuthorOfPublication2b5a3f0a-29c2-4ecd-a83f-50d0b99a4875
relation.isAuthorOfPublication.latestForDiscovery2b5a3f0a-29c2-4ecd-a83f-50d0b99a4875

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