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

2021-11Conference object Open access
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dc.contributor.authorInácio, Daniel
dc.contributor.authorAmado, Tiago
dc.contributor.authorSilva, Marta
dc.contributor.authorSobral, Daniel
dc.contributor.authorCunha, Carolina
dc.contributor.authorPamplona, Ana
dc.contributor.authorEnguita, Francisco
dc.contributor.authorGomes, Anita Q.
dc.contributor.authorSilva-Santos, Bruno
dc.date.accessioned2022-03-04T11:30:18Z
dc.date.available2022-03-04T11:30:18Z
dc.date.issued2021-11
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 the IL-17 or IFN-γ. We have previously found that one microRNA, miR-146a, maintains peripheral γδ T cell identity by inhibiting IFN-g production by the IL-17-committed CD27− gδ T cell subset. To further and more globally address the role of microRNAs in effector γδ T cell differentiation, we established a double reporter IL17-GFP:IFN-γ-YFP mouse strain and isolated pure IL-17+ and IFN-γ+ γδ T cell populations from the peripheral lymphoid organs to perform small RNA-sequencing. This allowed us to identify clearly 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 study further. We characterized the detailed expression pattern of each candidate microRNA in γδ T cell subsets throughout mouse ontogeny and upon gain-of-function studies in in vitro cultures of γδ T cells. 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. 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 in vivo 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 acting as an IFN-γ auto-repressor (miR-139-5p) or promoting functional plasticity (miR-7a-5p). Finally, miR-322-5p and miR-450b-3p, overexpressed in IL-17+ γδ T cells, may have therapeutic potential by modulating the production of IFNγ, whose levels are critical in anti-tumoral and anti-viral responses. These data demonstrate the impact of microRNAs on the 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, Silva M, Sobral D, Cunha C, Gomes AQ, et al. A key role for microRNAs in the development and functional differentiation of γδ T cell subsets. In: 9th International gd T cell Conference [online], Zhuhai (China), November 5-8, 2021.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/14376
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relation.publisherversionhttps://files.sciconf.cn/upload/file/20211104/20211104224812_29939.pdfpt_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.conferencePlaceZhuhaipt_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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