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A key role for microRNAs in the development and functional differentiation of γδ T cell subsets

2022-06Conference object Open access
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dc.contributor.authorInácio, Daniel
dc.contributor.authorAmado, Tiago
dc.contributor.authorSobral, Daniel
dc.contributor.authorCunha, Carolina
dc.contributor.authorSilva, Marta
dc.contributor.authorPamplona, Ana
dc.contributor.authorEnguita, Francisco
dc.contributor.authorGomes, Anita Q.
dc.contributor.authorSilva-Santos, Bruno
dc.date.accessioned2024-01-16T11:03:48Z
dc.date.available2024-01-16T11:03:48Z
dc.date.issued2022-06
dc.description.abstractThe ability of murine γδ T cells to rapidly produce the pro-inflammatory cytokines interleukin-17 (IL-17) or interferon-γ (IFN-γ) underlies their crucial roles in several (patho)physiological contexts. This capacity stems from a complex process of ‘developmental pre-programming’ in the thymus, after which a large fraction of γδ T cells migrate to peripheral sites already committed to producing either IL-17 or IFN-γ. To globally address the role of microRNAs in effector γδ T cell differentiation, we established a double reporter IL-17-GFP: IFN-γ-YFP mouse strain and isolated pure IL-17+ and IFN-γ+ γδ T cell populations from peripheral lymphoid organs to perform small RNA-sequencing. This allowed us to identify distinct microRNA signatures associated with cytokine expression in γδ T cells, from which we selected ten candidate microRNAs differentially expressed between IL-17+ and IFN-γ+ γδ T cells to functionally study further. Our results indicate that while some microRNAs, such as miR-128-3p and miR181a-5p, regulate γδ T cell development in the thymus, other candidates, including miR-7a-5p, miR-139-5p, miR-322-5p, and miR-450b-3p, modulate peripheral γδ T cell effector functions. Furthermore, using a miR-181a deficient mouse model, we have demonstrated that miR-181a, highly expressed in immature γδ T cell subsets in the thymus, shifts the in vivo IL-17/IFN-γ balance towards the IL-17 pathway in the neonatal thymus, which is further maintained in the periphery during adult life. These data demonstrate the impact of microRNAs on the development, differentiation, and functional identity of effector γδ T cell subsets, which may open new avenues for their manipulation in disease settings.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInácio D, Amado T, Sobral D, Cunha C, Silva M, Gomes AQ, et al. A key role for microRNAs in the development and functional differentiation of γδ T cell subsets. In: 2nd International EFIS/EJI FOR2799 Workshop – Receiving and Translating Signals via  TCR, Cefalu, Sicily (Italy), June 19-22, 2022.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/16894
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relation.publisherversionhttps://www.for2799.de/events/2nd-international-efis-eji-for2799-workshop-receiving-and-translating-signals-via-the-gd-tcr/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectMicroRNApt_PT
dc.subjectCytokinespt_PT
dc.titleA key role for microRNAs in the development and functional differentiation of γδ T cell subsetspt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceCefalupt_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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