Abstract
In recent years it has become clear that the therapeutic properties of bone marrow-derived mesenchymal stromal cells (MSC) are related not only to their ability to differentiate into different lineages but also to their capacity to suppress the immune response. We here studied the influence of MSC on macrophage function. Using mouse thioglycolate-elicited peritoneal macrophages (M) stimulated with LPS, we found that MSC markedly suppressed the production of the inflammatory cytokines TNF-α, IL-6, IL-12p70 and interferon-γ while increased the production of IL-10 and IL-12p40. Similar results were observed using supernatants from MSC suggesting that factor(s) constitutively released by MSC are involved. Supporting a role for PGE2 we observed that acetylsalicylic acid impaired the ability of MSC to inhibit the production of inflammatory cytokines and to stimulate the production of IL-10 by LPS-stimulated M. Moreover, we found that MSC constitutively produce PGE2 at levels able to inhibit the production of TNF-α and IL-6 by activated M. MSC also inhibited the up-regulation of CD86 and MHC class II in LPS-stimulated M impairing their ability to activate antigen-specific T CD4+ cells. On the other hand, they stimulated the uptake of apoptotic thymocytes by M. Of note, MSC turned M into cells highly susceptible to infection with the parasite Trypanosoma cruzi increasing more than 5-fold the rate of M infection. Using a model of inflammation triggered by s.c. implantation of glass cylinders, we found that MSC stimulated the recruitment of macrophages which showed a low expression of CD86 and the MHC class II molecule Iab and a high ability to produce IL-10 and IL-12p40, but not IL-12 p70. In summary, our results suggest that MSC switch M into a regulatory profile characterized by a low ability to produce inflammatory cytokines, a high ability to phagocyte apoptotic cells, and a marked increase in their susceptibility to infection by intracellular pathogens.
Highlights
Bone marrow-derived mesenchymal stromal cells (MSC) are pluripotent adult stromal cells able to differentiate into different cell types such as osteoblasts, chondrocytes and adipocytes [1]
We show here that MSC turns activated macrophages into a regulatory profile characterized by a low ability to produce inflammatory cytokines, a high ability to phagocyte apoptotic cells, and a dramatic increase in their susceptibility to infection with the parasite Trypanosoma cruzi (T. cruzi)
Because our results support the notion that macrophages differentiate into a regulatory-like profile under the influence of MSC, we examined whether MSC increased the susceptibility of M to T. cruzi infection
Summary
Bone marrow-derived mesenchymal stromal cells (MSC) are pluripotent adult stromal cells able to differentiate into different cell types such as osteoblasts, chondrocytes and adipocytes [1]. MSC inhibit cytotoxicity and production of interferon-c by NK cells [10,11], and exert a potent immunosuppressive effect on T cells They suppress T-cell proliferation induced by alloantigens, mitogens and soluble antigens [12,13,14]. The mechanisms underlying the immunosuppressive effects mediated by MSC are not fully defined, but they appear to be largely mediated by a number of soluble factors produced by MSC, either constitutively or in response to paracrine signals derived from leukocytes. These soluble mediators include transforming growth factor-b1 (TGFb1), hepatocyte growth factor, PGE2, indoleamine 2,3-dioxygenase (IDO), haem oxygenase-1, soluble HLA-G5, IL10 and IL-6 [4,5,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
