Single and combined effect of retinoic acid and rapamycin modulate the generation, activity and homing potential of induced human regulatory T cells

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dc.contributor.authorCandia, E.
dc.contributor.authorReyes, P.
dc.contributor.authorCovian, C.
dc.contributor.authorRodriguez, F.
dc.contributor.authorWainstein, N.
dc.contributor.authorMorales, J.
dc.contributor.authorMosso, C.
dc.contributor.authorRosemblatt, M.
dc.contributor.authorFierro, J.A.
dc.date.accessioned2018-01-05T14:47:02Z
dc.date.available2018-01-05T14:47:02Z
dc.date.issued2017-07
dc.descriptionIndexación: Web of Science; Scopus.es_CL
dc.description.abstractAdoptive transfer of CD4+CD25+FOXP3+ regulatory T cells (Treg cells) has been successfully utilized to treat graft versus host disease and represents a promising strategy for the treatment of autoimmune diseases and transplant rejection. The aim of this study was to evaluate the effects of all-trans retinoic acid (atRA) and rapamycin (RAPA) on the number, phenotype, homing markers expression, DNA methylation, and function of induced human Treg cells in short-term cultures. Naive T cells were polyclonally stimulated and cultured for five days in the presence of different combinations of IL-2, TGF-β1, atRA and RAPA. The resulting cells were characterized by the expression of FOXP3, activation, surface and homing markers. Methylation of the Conserved Non-coding Sequence 2 was also evaluated. Functional comparison of the different culture conditions was performed by suppression assays in vitro. Culturing naive human T cells with IL-2/TGFβ1 resulted in the generation of 54.2% of Treg cells (CD4+CD25+FOXP3+) whereas the addition of 100 nM atRA increased the yield of Treg cells to 66% (p = 0.0088). The addition of RAPA did not increase the number of Treg cells in any of these settings. Treg cells generated in the presence of atRA had an increased expression of the β7 integrin to nearly 100% of the generated Treg cells, while RAPA treated cells showed enhanced expression of CXCR4. The differential expression of homing molecules highlights the possibility of inducing Treg cells with differential organ-specific homing properties. Neither atRA nor RAPA had an effect on the highly methylated CNS2 sites, supporting reports that their contribution to the lineage stability of Treg cells is not mediated by methylation changes in this locus. Treg cells generated in the presence of RAPA show the most potent suppression effect on the proliferation of effector cells.es_CL
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182009
dc.identifier.citationPLoS ONE, 12 (7), art. no. e0182009es_CL
dc.identifier.issn1932-6203
dc.identifier.otherDOI: 10.1371/journal.pone.0182009
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/5035
dc.language.isoenes_CL
dc.publisherPublic Library of Sciencees_CL
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAdolescentes_CL
dc.subjectAdultes_CL
dc.subjectAntineoplastic Agentses_CL
dc.subjectCells, Culturedes_CL
dc.subjectCpG Islandses_CL
dc.subjectDNA Methylationes_CL
dc.subjectDrug Synergismes_CL
dc.subjectFlow Cytometryes_CL
dc.subjectForkhead Transcription Factorses_CL
dc.subjectHumanses_CL
dc.subjectInterleukin-2es_CL
dc.subjectInterleukin-2 Receptor alpha Subunites_CL
dc.subjectSirolimuses_CL
dc.subjectT-Lymphocyteses_CL
dc.subjectT-Lymphocytes, Regulatoryes_CL
dc.subjectTransforming Growth Factor beta1es_CL
dc.subjectTretinoines_CL
dc.subjectYoung Adultes_CL
dc.titleSingle and combined effect of retinoic acid and rapamycin modulate the generation, activity and homing potential of induced human regulatory T cellses_CL
dc.typeArtículoes_CL
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