MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells

Abstract The mechanisms underlying mesenchymal stem cells’ (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early...

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Autores principales:	Carolina Lavini-Ramos, Hernandez Moura Silva, Alessandra Soares-Schanoski, Sandra Maria Monteiro, Ludmila Rodrigues Pinto Ferreira, Ana Paula Pacanaro, Samirah Gomes, Janaína Batista, Kellen Faé, Jorge Kalil, Verônica Coelho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/580b000eb41d4ca581e73640fbe8af80
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spelling	oai:doaj.org-article:580b000eb41d4ca581e73640fbe8af802021-12-02T12:30:54ZMMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells10.1038/s41598-017-00923-02045-2322https://doaj.org/article/580b000eb41d4ca581e73640fbe8af802017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00923-0https://doaj.org/toc/2045-2322Abstract The mechanisms underlying mesenchymal stem cells’ (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73+Foxp3+Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.Carolina Lavini-RamosHernandez Moura SilvaAlessandra Soares-SchanoskiSandra Maria MonteiroLudmila Rodrigues Pinto FerreiraAna Paula PacanaroSamirah GomesJanaína BatistaKellen FaéJorge KalilVerônica CoelhoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carolina Lavini-Ramos Hernandez Moura Silva Alessandra Soares-Schanoski Sandra Maria Monteiro Ludmila Rodrigues Pinto Ferreira Ana Paula Pacanaro Samirah Gomes Janaína Batista Kellen Faé Jorge Kalil Verônica Coelho MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
description	Abstract The mechanisms underlying mesenchymal stem cells’ (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73+Foxp3+Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.
format	article
author	Carolina Lavini-Ramos Hernandez Moura Silva Alessandra Soares-Schanoski Sandra Maria Monteiro Ludmila Rodrigues Pinto Ferreira Ana Paula Pacanaro Samirah Gomes Janaína Batista Kellen Faé Jorge Kalil Verônica Coelho
author_facet	Carolina Lavini-Ramos Hernandez Moura Silva Alessandra Soares-Schanoski Sandra Maria Monteiro Ludmila Rodrigues Pinto Ferreira Ana Paula Pacanaro Samirah Gomes Janaína Batista Kellen Faé Jorge Kalil Verônica Coelho
author_sort	Carolina Lavini-Ramos
title	MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
title_short	MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
title_full	MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
title_fullStr	MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
title_full_unstemmed	MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
title_sort	mmp9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/580b000eb41d4ca581e73640fbe8af80
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_version_	1718394279853817856

MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells

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