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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorLAVINI-RAMOS, Carolina
dc.contributor.authorSILVA, Hernandez Moura
dc.contributor.authorSOARES-SCHANOSKI, Alessandra
dc.contributor.authorMONTEIRO, Sandra Maria
dc.contributor.authorFERREIRA, Ludmila Rodrigues Pinto
dc.contributor.authorPACANARO, Ana Paula
dc.contributor.authorGOMES, Samirah
dc.contributor.authorBATISTA, Janaina
dc.contributor.authorFAE, Kellen
dc.contributor.authorKALIL, Jorge
dc.contributor.authorCOELHO, Veronica
dc.date.accessioned2017-06-09T15:18:14Z
dc.date.available2017-06-09T15:18:14Z
dc.date.issued2017
dc.description.abstractThe 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.
dc.description.indexMEDLINE
dc.description.sponsorshipCNPq [830058/2008-7]
dc.identifier.citationSCIENTIFIC REPORTS, v.7, article ID 874, 15p, 2017
dc.identifier.doi10.1038/s41598-017-00923-0
dc.identifier.issn2045-2322
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/19914
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.relation.ispartofScientific Reports
dc.rightsopenAccess
dc.rights.holderCopyright NATURE PUBLISHING GROUP
dc.subject.otherversus-host-disease
dc.subject.otherregulatory t-cells
dc.subject.otherbone-marrow
dc.subject.otherindoleamine 2,3-dioxygenase
dc.subject.otherlymphocyte-proliferation
dc.subject.otherstromal cells
dc.subject.otherifn-gamma
dc.subject.otherprotein networks
dc.subject.otherprogenitor cells
dc.subject.othergene-expression
dc.subject.wosMultidisciplinary Sciences
dc.titleMMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryHolanda
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisonl
hcfmusp.author.externalLAVINI-RAMOS, Carolina:Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Immunol, Sao Paulo, Brazil; Iii INCT Natl Inst Sci & Technol, Inst Invest Immunol, Sao Paulo, Brazil
hcfmusp.author.externalSILVA, Hernandez Moura:Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Immunol, Sao Paulo, Brazil; Iii INCT Natl Inst Sci & Technol, Inst Invest Immunol, Sao Paulo, Brazil; NYU, Sch Med, Skirball Inst, Mol Pathogenesis Program,Kimmel Ctr Biol & Med, New York, NY 10016 USA
hcfmusp.author.externalBATISTA, Janaina:Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Immunol, Sao Paulo, Brazil; Iii INCT Natl Inst Sci & Technol, Inst Invest Immunol, Sao Paulo, Brazil
hcfmusp.author.externalFAE, Kellen:Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Immunol, Sao Paulo, Brazil; Iii INCT Natl Inst Sci & Technol, Inst Invest Immunol, Sao Paulo, Brazil; Crucell Holland & BV, Bacterial Vaccines Discovery & Early Dev, Leiden, Netherlands
hcfmusp.citation.scopus11
hcfmusp.contributor.author-fmusphcALESSANDRA SOARES SCHANOSKI
hcfmusp.contributor.author-fmusphcSANDRA MARIA MONTEIRO
hcfmusp.contributor.author-fmusphcLUDMILA RODRIGUES PINTO FERREIRA CAMARGO
hcfmusp.contributor.author-fmusphcANA PAULA PACANARO
hcfmusp.contributor.author-fmusphcSAMIRAH ABREU GOMES
hcfmusp.contributor.author-fmusphcJORGE ELIAS KALIL FILHO
hcfmusp.contributor.author-fmusphcVERONICA PORTO CARREIRO DE VASCONCELLOS COELHO
hcfmusp.description.articlenumber874
hcfmusp.description.volume7
hcfmusp.origemWOS
hcfmusp.origem.pubmed28408751
hcfmusp.origem.scopus2-s2.0-85018160559
hcfmusp.origem.wosWOS:000399036900015
hcfmusp.publisher.cityLONDON
hcfmusp.publisher.countryENGLAND
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