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Signature cytokine-associated transcriptome analysis of effector γδ T cells identifies subset-specific regulators of peripheral activation

dc.contributor.authorInácio, Daniel
dc.contributor.authorAmado, Tiago
dc.contributor.authorPamplona, Ana
dc.contributor.authorSobral, Daniel
dc.contributor.authorCunha, Carolina
dc.contributor.authorSantos, Rita F.
dc.contributor.authorOliveira, Liliana
dc.contributor.authorRouquié, Nelly
dc.contributor.authorCarmo, Alexandre M.
dc.contributor.authorLesourne, Renaud
dc.contributor.authorGomes, Anita Q.
dc.contributor.authorSilva-Santos, Bruno
dc.date.accessioned2025-11-14T15:17:14Z
dc.date.available2025-11-14T15:17:14Z
dc.date.issued2025-01-29
dc.description.abstractγδ T cells producing either interleukin-17A (γδ cells) or interferon-γ (γδ cells) are generated in the mouse thymus, but the molecular regulators of their peripheral functions are not fully characterized. Here we established an Il17a-GFP:Ifng-YFP double-reporter mouse strain to analyze at unprecedented depth the transcriptomes of pure γδ cell versus γδ cell populations from peripheral lymph nodes. Within a very high fraction of differentially expressed genes, we identify a panel of 20 new signature genes in steady-state γδ cells versus γδ cells, which we further validate in models of experimental autoimmune encephalomyelitis and cerebral malaria, respectively. Among the signature genes, we show that the co-receptor CD6 and the signaling protein Themis promote the activation and proliferation of peripheral γδ cells in response to T cell antigen receptor stimulation in vitro and to Plasmodium infection in vivo. This resource can help to understand the distinct activities of effector γδ T cell subsets in pathophysiology.eng
dc.description.sponsorshipThe project leading to these results has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 646701 to B.S.-S.), ‘la Caixa’ Foundation under project code LCF/PR/HR24/00929 (to B.S.-S.), Fundação para a Ciência e Tecnologia, Ministério da Ciência, Tecnologia e Ensino Superior, Portugal (PTDC/MED-IMU/32296/2017 to A.M.C.; SFRH/BD/145352/2019 to D.I.; Decree-law number 57/2016, as amended by the Law number 57/2017 to A.P.) and Fondation pour la Recherche Médicale (to R.L.).
dc.identifier.citationNat Immunol. 2025 Mar;26(3):497-510. doi: 10.1038/s41590-024-02073-8. Epub 2025 Jan 29
dc.identifier.doi10.1038/s41590-024-02073-8
dc.identifier.eissn1529-2916
dc.identifier.issn1529-2908
dc.identifier.pmid39881001
dc.identifier.urihttp://hdl.handle.net/10400.18/10613
dc.language.isoeng
dc.peerreviewedyes
dc.publisherNature Research
dc.relationPTDC/MED-IMU/32296/2017
dc.relationSFRH/BD/145352/2019
dc.relation.hasversionhttps://www.nature.com/articles/s41590-024-02073-8
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectγδ T cells
dc.subjectTranscriptome Analysis
dc.subjectCytokines
dc.subjectSubset-Specific Regulators
dc.subjectPeripheral Activation
dc.subjectGenetics
dc.subjectImmunology
dc.titleSignature cytokine-associated transcriptome analysis of effector γδ T cells identifies subset-specific regulators of peripheral activationeng
dc.typejournal article
dcterms.referenceshttps://static-content.springer.com/esm/art%3A10.1038%2Fs41590-024-02073-8/MediaObjects/41590_2024_2073_MOESM1_ESM.pdf
dcterms.referenceshttps://static-content.springer.com/esm/art%3A10.1038%2Fs41590-024-02073-8/MediaObjects/41590_2024_2073_MOESM2_ESM.xlsx
dspace.entity.typePublication
oaire.citation.endPage510
oaire.citation.issue3
oaire.citation.startPage497
oaire.citation.titleNature Immunology
oaire.citation.volume26
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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