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

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.accessioned2024-01-16T10:45:51Z
dc.date.available2024-01-16T10:45:51Z
dc.date.issued2022-04
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 thymic process of ‘developmental pre-programming’, after which a large fraction of γδ T cells migrates to peripheral sites already committed to producing IL-17 or IFN-γ. We have previously found that miR-146a maintains the cell identity of peripheral IL-17-committed gδ T cells by inhibiting IFN-g production. To further address the role of microRNAs in γδ T cell differentiation, we isolated pure IL-17+ and IFN-γ+ γδ T cell populations from the peripheral lymphoid organs of a double reporter IL-17-GFP: IFN-γ-YFP mouse strain 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 microRNAs differentially expressed between IL-17+ and IFN-γ+ subsets to further characterize. We first analyzed the expression pattern of each candidate microRNA in γδ T cell subsets throughout mouse ontogeny and upon gain-of-function studies in in vitro γδ T cell cultures. Our results indicate that while some microRNAs regulate γδ T cell development in the thymus, other candidates modulate their peripheral effector functions. More specifically, using a miR-181a deficient mouse model, we have found that miR-181a, highly expressed in immature γδ T cell subsets in the thymus, shifts the IL-17/IFN-γ balance towards the IL-17-pathway in neonatal life, which is further maintained in the periphery during adult life. On the other hand, miR-7a-5p and miR-139-5p, overexpressed in peripheral IFN-g+ γδ T cells, regulate peripheral γδ T cell effector functions, either promoting functional plasticity or acting as an IFN-γ auto-repressor, respectively. Finally, miR-322-5p and miR-450b-3p, overexpressed in IL-17+ γδ T cells, may have therapeutic potential by modulating IFN-γ levels, which are critical in anti-tumoral and antiviral responses.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: XLVII Annual Meeting of the Portuguese Society of Immunology – At the crossroads of Human Immunology / Workshop of the Iberian Flow Cytometry Society, Reitoria da Universidade Nova de Lisboa, April 20-22, 2022.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/16893
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relation.publisherversionhttps://www.spimunologia.org/news/spi-2022/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.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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