Mesenchymal Stromal Cells Induce Peculiar Alternatively Activated Macrophages Capable of Dampening Both Innate and Adaptive Immune Responses. (14th April 2016)

• Record Type: Journal Article
• Authors: Chiossone, Laura; Conte, Romana; Spaggiari, Grazia Maria; Serra, Martina; Romei, Cristina; Bellora, Francesca; Becchetti, Flavio; Andaloro, Antonio; Moretta, Lorenzo; Bottino, Cristina
• Is Part Of: Stem cells. Volume 34:Number 7(2016:Jul.)
• Page Start: 1909
• Page End: 1921
• Publication Date: 2016-04-14
• Subjects: Mesenchymal stromal cells -- Macrophages -- NK cells -- T cells -- PGE2; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2369
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Mesenchymal stromal cells (MSCs) support hematopoiesis and exert immunoregulatory activities. Here, we analyzed the functional outcome of the interactions between MSCs and monocytes/macrophages. We showed that MSCs supported the survival of monocytes that underwent differentiation into macrophages, in the presence of macrophage colony-stimulating factor. However, MSCs skewed their polarization toward a peculiar M2-like functional phenotype (M MSC ), through a prostaglandin E2-dependent mechanism. M MSC were characterized by high expression of scavenger receptors, increased phagocytic capacity, and high production of interleukin (IL)-10 and transforming growth factor-β. These cytokines contributed to the immunoregulatory properties of M MSC, which differed from those of typical IL-4-induced macrophages (M2). In particular, interacting with activated natural killer (NK) cells, M MSC inhibited both the expression of activating molecules such as NKp44, CD69, and CD25 and the production of IFNγ, while M2 affected only IFNγ production. Moreover, M MSC inhibited the proliferation of CD8 + T cells in response to allogeneic stimuli and induced the expansion of regulatory T cells (Tregs). Toll-like receptor engagement reverted the phenotypic and functional features of M MSC to those of M1 immunostimulatory/proinflammatory macrophages. Overall our data show that MSCs induce the generation of a novel type of alternatively activated macrophages capable of suppressing both innate and adaptive immune responses. These findings may help to better understand the role of MSCs in healthy tissues and inflammatory diseases including cancer, and provide clues for novel therapeutic approaches. Abstract : Mesenchymal stromal cells (MSC) induce the generation of a novel subset of alternatively activated macrophages (M MSC ), via the release of PGE2. M MSC are characterized by high expression of CD14, CD16, CD206, HLA-II, CD11b, CD163, and CD209 and secrete high amounts of IL-1β, IL-10, and TGF-β. These cytokines contribute to the immunoregulatory properties of M MSC . Interacting with autologous activated NK cells, M MSC inhibit both the expression of activating molecules such as NKp44, CD69, and CD25 and the production of IFNγ. Moreover, M MSC inhibit the proliferation of CD8 + T cells and induce the expansion of regulatory T cells (Treg). LPS revert the phenotypic and functional features of M MSC to those of M1 immunostimulatory/proinflammatory macrophages.