Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPLAVINI-RAMOS, CarolinaSILVA, Hernandez MouraSOARES-SCHANOSKI, AlessandraMONTEIRO, Sandra MariaFERREIRA, Ludmila Rodrigues PintoPACANARO, Ana PaulaGOMES, SamirahBATISTA, JanainaFAE, KellenKALIL, JorgeCOELHO, Veronica2017-06-092017-06-092017SCIENTIFIC REPORTS, v.7, article ID 874, 15p, 20172045-2322https://observatorio.fm.usp.br/handle/OPI/19914The 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.engopenAccessversus-host-diseaseregulatory t-cellsbone-marrowindoleamine 2,3-dioxygenaselymphocyte-proliferationstromal cellsifn-gammaprotein networksprogenitor cellsgene-expressionarticleCopyright NATURE PUBLISHING GROUP10.1038/s41598-017-00923-0Multidisciplinary Sciences