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https://observatorio.fm.usp.br/handle/OPI/19914
Title: | MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells |
Authors: | LAVINI-RAMOS, Carolina; SILVA, Hernandez Moura; SOARES-SCHANOSKI, Alessandra; MONTEIRO, Sandra Maria; FERREIRA, Ludmila Rodrigues Pinto; PACANARO, Ana Paula; GOMES, Samirah; BATISTA, Janaina; FAE, Kellen; KALIL, Jorge; COELHO, Veronica |
Citation: | SCIENTIFIC REPORTS, v.7, article ID 874, 15p, 2017 |
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-gamma and TNF-alpha 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. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MCM Artigos e Materiais de Revistas Científicas - HC/ICHC Artigos e Materiais de Revistas Científicas - HC/InCor Artigos e Materiais de Revistas Científicas - LIM/19 Artigos e Materiais de Revistas Científicas - LIM/29 |
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