title: Human Bone Marrow-Derived Mesenchymal Stromal Cells Differentially Inhibit Cytokine Production by Peripheral Blood Monocytes Subpopulations and Myeloid Dendritic Cells.
abstract: The immunosuppressive properties of mesenchymal stromal/stem cells (MSC) rendered them an attractive therapeutic approach for immune disorders and an increasing body of evidence demonstrated their clinical value. However, the influence of MSC on the function of specific immune cell populations, namely, monocyte subpopulations, is not well elucidated. Here, we investigated the influence of human bone marrow MSC on the cytokine and chemokine expression by peripheral blood classical, intermediate and nonclassical monocytes, and myeloid dendritic cells (mDC), stimulated with lipopolysaccharide plus interferon (IFN)γ. We found that MSC effectively inhibit tumor necrosis factor- (TNF-) α and macrophage inflammatory protein- (MIP-) 1β protein expression in monocytes and mDC, without suppressing CCR7 and CD83 protein expression. Interestingly, mDC exhibited the highest degree of inhibition, for both TNF-α and MIP-1β, whereas the reduction of TNF-α expression was less marked for nonclassical monocytes. Similarly, MSC decreased mRNA levels of interleukin- (IL-) 1β and IL-6 in classical monocytes, CCL3, CCL5, CXCL9, and CXCL10 in classical and nonclassical monocytes, and IL-1β and CXCL10 in mDC. MSC do not impair the expression of maturation markers in monocytes and mDC under our experimental conditions; nevertheless, they hamper the proinflammatory function of monocytes and mDC, which may impede the development of inflammatory immune responses.
authors.affiliation: Blood and Transplantation Center of Coimbra, Portuguese Institute of the Blood and Transplantation, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Laranjeira
authors.affiliation: Blood and Transplantation Center of Coimbra, Portuguese Institute of the Blood and Transplantation, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, Portugal ; QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Gomes
authors.affiliation: Blood and Transplantation Center of Coimbra, Portuguese Institute of the Blood and Transplantation, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, Portugal.
authors.forename: Susana
authors.identifier: 0000-0002-2821-601X
authors.initials: S
authors.lastname: Pedreiro
authors.affiliation: Blood and Transplantation Center of Coimbra, Portuguese Institute of the Blood and Transplantation, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, Portugal ; Signal Transduction Laboratory, Center of Cellular Biology, SACS and Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Monia
authors.initials: M
authors.lastname: Pedrosa
authors.affiliation: Blood and Transplantation Center of Coimbra, Portuguese Institute of the Blood and Transplantation, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, Portugal.
authors.forename: Antonio
authors.initials: A
authors.lastname: Martinho
authors.affiliation: Cell2B Advanced Therapeutics, SA, Biocant Park, Núcleo 04, Lote 4A, 3060-197 Cantanhede, Portugal.
authors.forename: Brigida
authors.initials: B
authors.lastname: Antunes
authors.affiliation: Cell2B Advanced Therapeutics, SA, Biocant Park, Núcleo 04, Lote 4A, 3060-197 Cantanhede, Portugal.
authors.forename: Tania
authors.initials: T
authors.lastname: Ribeiro
authors.affiliation: Cell2B Advanced Therapeutics, SA, Biocant Park, Núcleo 04, Lote 4A, 3060-197 Cantanhede, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Santos
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Rosario
authors.initials: R
authors.lastname: Domingues
authors.affiliation: Serviço de Transplantação de Progenitores Hematopoiéticos (UTM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisboa, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Abecasis
authors.affiliation: Blood and Transplantation Center of Coimbra, Portuguese Institute of the Blood and Transplantation, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, Portugal.
authors.forename: Helder
authors.initials: H
authors.lastname: Trindade
authors.affiliation: Blood and Transplantation Center of Coimbra, Portuguese Institute of the Blood and Transplantation, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861 Coimbra, Portugal.
authors.forename: Artur
authors.initials: A
authors.lastname: Paiva