TGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation

Abstract Regulatory T cells (Tregs) are essential regulators of immune tolerance. atRA and TGF-β can inhibit the polarization of naïve T cells into inflammatory Th17 cells, favoring the generation of stable iTregs, however the regulatory mechanisms involved are not fully understood. In this context,...

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Autores principales:	Josiane Lilian dos Santos Schiavinato, Rodrigo Haddad, Felipe Saldanha-Araujo, João Baiochi, Amélia Goes Araujo, Priscila Santos Scheucher, Dimas Tadeu Covas, Marco Antonio Zago, Rodrigo Alexandre Panepucci
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5558f06850b1423887977055c6ff49cd
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spelling	oai:doaj.org-article:5558f06850b1423887977055c6ff49cd2021-12-02T11:52:41ZTGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation10.1038/s41598-017-03456-82045-2322https://doaj.org/article/5558f06850b1423887977055c6ff49cd2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03456-8https://doaj.org/toc/2045-2322Abstract Regulatory T cells (Tregs) are essential regulators of immune tolerance. atRA and TGF-β can inhibit the polarization of naïve T cells into inflammatory Th17 cells, favoring the generation of stable iTregs, however the regulatory mechanisms involved are not fully understood. In this context, the roles of individual microRNAs in Tregs are largely unexplored. Naïve T cells were immunomagnetically isolated from umbilical cord blood and activated with anti-human CD2/CD3/CD28 beads in the presence of IL-2 alone (CD4Med) or with the addition of TGF-β and atRA (CD4TGF/atRA). As compared to CD4Med, the CD4TGF/atRA condition allowed the generation of highly suppressive CD4+CD25hiCD127−FOXP3hi iTregs. Microarray profiling allowed the identification of a set of microRNAs that are exclusively expressed upon TGF-β/atRA treatment and that are predicted to target a set of transcripts concordantly downregulated. This set of predicted targets were enriched for central components of IL-6/JAK/STAT and AKT-mTOR signaling, whose inhibition is known to play important roles in the generation and function of regulatory lymphocytes. Finally, we show that mimics of exclusively expressed miRs (namely miR-1299 and miR-30a-5p) can reduce the levels of its target transcripts, IL6R and IL6ST (GP130), and increase the percentage of FoxP3+ cells among CD4+CD25+/hi cells.Josiane Lilian dos Santos SchiavinatoRodrigo HaddadFelipe Saldanha-AraujoJoão BaiochiAmélia Goes AraujoPriscila Santos ScheucherDimas Tadeu CovasMarco Antonio ZagoRodrigo Alexandre PanepucciNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Josiane Lilian dos Santos Schiavinato Rodrigo Haddad Felipe Saldanha-Araujo João Baiochi Amélia Goes Araujo Priscila Santos Scheucher Dimas Tadeu Covas Marco Antonio Zago Rodrigo Alexandre Panepucci TGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation
description	Abstract Regulatory T cells (Tregs) are essential regulators of immune tolerance. atRA and TGF-β can inhibit the polarization of naïve T cells into inflammatory Th17 cells, favoring the generation of stable iTregs, however the regulatory mechanisms involved are not fully understood. In this context, the roles of individual microRNAs in Tregs are largely unexplored. Naïve T cells were immunomagnetically isolated from umbilical cord blood and activated with anti-human CD2/CD3/CD28 beads in the presence of IL-2 alone (CD4Med) or with the addition of TGF-β and atRA (CD4TGF/atRA). As compared to CD4Med, the CD4TGF/atRA condition allowed the generation of highly suppressive CD4+CD25hiCD127−FOXP3hi iTregs. Microarray profiling allowed the identification of a set of microRNAs that are exclusively expressed upon TGF-β/atRA treatment and that are predicted to target a set of transcripts concordantly downregulated. This set of predicted targets were enriched for central components of IL-6/JAK/STAT and AKT-mTOR signaling, whose inhibition is known to play important roles in the generation and function of regulatory lymphocytes. Finally, we show that mimics of exclusively expressed miRs (namely miR-1299 and miR-30a-5p) can reduce the levels of its target transcripts, IL6R and IL6ST (GP130), and increase the percentage of FoxP3+ cells among CD4+CD25+/hi cells.
format	article
author	Josiane Lilian dos Santos Schiavinato Rodrigo Haddad Felipe Saldanha-Araujo João Baiochi Amélia Goes Araujo Priscila Santos Scheucher Dimas Tadeu Covas Marco Antonio Zago Rodrigo Alexandre Panepucci
author_facet	Josiane Lilian dos Santos Schiavinato Rodrigo Haddad Felipe Saldanha-Araujo João Baiochi Amélia Goes Araujo Priscila Santos Scheucher Dimas Tadeu Covas Marco Antonio Zago Rodrigo Alexandre Panepucci
author_sort	Josiane Lilian dos Santos Schiavinato
title	TGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation
title_short	TGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation
title_full	TGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation
title_fullStr	TGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation
title_full_unstemmed	TGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation
title_sort	tgf-beta/atra-induced tregs express a selected set of micrornas involved in the repression of transcripts related to th17 differentiation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5558f06850b1423887977055c6ff49cd
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TGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation

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