title: Prostaglandin E2 plays a key role in the immunosuppressive properties of adipose and bone marrow tissue-derived mesenchymal stromal cells.
abstract: Mesenchymal stromal cells (MSCs) have important immunosuppressive properties, but the mechanisms and soluble factors involved in these effects remain unclear. We have studied prostaglandin-E2 (PGE2) as a possible candidate implied in adipose tissue-derived MSCs (Ad-MSCs) immunosuppressive properties over dendritic cells and T lymphocytes, compared to bone marrow derived MSCs (BM-MSCs). We found that both MSCs inhibited the maturation of myeloid-DCs and plasmocytoid-DCs. High levels of PGE2 were detected in DCs/MSCs co-cultures. Its blockade with indomethacin (IDM) allowed plasmocytoid-DCs but not myeloid-DCs maturation. Additionally, high levels of PGE2 were found in co-cultures in which Ad-MSCs or BM-MSCs inhibited activated T cells proliferation and pro-inflammatory cytokines production. PGE2 blockade by IDM preserved T lymphocytes proliferation but did not restore the pro-inflammatory cytokines secretion. However, an increased expression of transcription factors and cytokines genes involved in the Th1/Th2 differentiation pathway was detected in the T cells co-cultured with Ad-MSCs, but not with BM-MSCs. In conclusion, we propose that PGE2 is a soluble factor mediating most of the immunosuppressive effects of Ad-MSCs and BM-MSCs over p-DCs maturation and activated T lymphocytes proliferation and cytokine secretion.
authors.affiliation: Hematopoiesis and Gene Therapy Division, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas andCentro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain. rosamaria.yanez@ciemat.es
authors.forename: Rosa
authors.initials: R
authors.lastname: Yañez
authors.forename: Alberto
authors.initials: A
authors.lastname: Oviedo
authors.forename: Montserrat
authors.initials: M
authors.lastname: Aldea
authors.forename: Juan A
authors.initials: JA
authors.lastname: Bueren
authors.forename: María L
authors.initials: ML
authors.lastname: Lamana
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015232:Dinoprostone / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D016130:Immunophenotyping; D007213:Indomethacin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D008934:Mitogens; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D015232:Dinoprostone; D007213:Indomethacin