title: Amniotic membrane mesenchymal cells-derived factors skew T cell polarization toward Treg and downregulate Th1 and Th17 cells subsets.
abstract: We previously demonstrated that cells derived from the mesenchymal layer of the human amniotic membrane (hAMSC) and their conditioned medium (CM-hAMSC) modulate lymphocyte proliferation in a dose-dependent manner. In order to understand the mechanisms involved in immune regulation exerted by hAMSC, we analyzed the effects of CM-hAMSC on T-cell polarization towards Th1, Th2, Th17, and T-regulatory (Treg) subsets. We show that CM-hAMSC equally suppresses the proliferation of both CD4(+) T-helper (Th) and CD8(+) cytotoxic T-lymphocytes. Moreover, we prove that the CM-hAMSC inhibitory ability affects both central (CD45RO(+)CD62L(+)) and effector memory (CD45RO(+)CD62L(-)) subsets. We evaluated the phenotype of CD4(+) cells in the MLR setting and showed that CM-hAMSC significantly reduced the expression of markers associated to the Th1 (T-bet(+)CD119(+)) and Th17 (RORγt(+)CD161(+)) populations, while having no effect on the Th2 population (GATA3(+)CD193(+)/GATA3(+)CD294(+)cells). T-cell subset modulation was substantiated through the analysis of cytokine release for 6 days during co-culture with alloreactive T-cells, whereby we observed a decrease in specific subset-related cytokines, such as a decrease in pro-inflammatory, Th1-related (TNFα, IFNγ, IL-1β), Th2 (IL-5, IL-6), Th9 (IL-9), and Th17 (IL-17A, IL-22). Furthermore, CM-hAMSC significantly induced the Treg compartment, as shown by an induction of proliferating CD4(+)FoxP3(+) cells, and an increase of CD25(+)FoxP3(+) and CD39(+)FoxP3(+) Treg in the CD4(+) population. Induction of Treg cells was corroborated by the increased secretion of TGF-β. Taken together, these data strengthen the findings regarding the immunomodulatory properties of CM-hAMSC derived from human amniotic membrane MSC, and in particular provide insights into their effect on regulation of T cell polarization.
authors.affiliation: Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, Via Bissolati, 57, I-25124, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pianta
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bonassi Signoroni
authors.forename: Ivan
authors.initials: I
authors.lastname: Muradore
authors.forename: Melissa Francis
authors.initials: MF
authors.lastname: Rodrigues
authors.forename: Daniele
authors.initials: D
authors.lastname: Rossi
authors.forename: Antonietta
authors.initials: A
authors.lastname: Silini
authors.forename: Ornella
authors.initials: O
authors.lastname: Parolini
mesh_terms: D000650:Amnion / Q000737:chemistry* / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000737:chemistry* / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta