Myeloid-derived suppressor cells regulate B-cell responses

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dc.contributor.advisor Hartl, Dominik (Prof. Dr.) Nobre Lelis, Felipe Jose 2017-02-09T09:36:24Z 2017-02-09T09:36:24Z 2019-02-01
dc.identifier.other 516870068 de_DE
dc.identifier.uri de_DE
dc.description.abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell group, which share close phenotypical similarities with conventional myeloid cells. In contrast to conventional myeloid cells, MDSCs have the ability to suppress other immune cells. MDSCs have been reported to suppress dendritic cells (DCs), natural killer (NK) and natural killer T cells (NKT) cells. However, the “gold standard” to characterize and discriminate them from other myeloid cells is the ability to suppress T-cell function. MDSCs apply multiple mechanisms of suppression, including production of reactive oxygen and nitrogen species, arginase-1 and production of several immunomodulatory cytokines. MDSCs have been described to arise in several forms of cancer, where they correlate with poor prognosis. Beyond cancer, MDSCs have been involved in chronic inflammatory and autoimmune diseases. However, in these situations the effects of MDSCs are still controversial and need further investigation. B cells are the key players of the humoral adaptive immune response. Their main function is to produce antibodies. B cells are involved in eliminating mainly extracellular invasive pathogens. Moreover, they are important modulators of several diseases, such as systemic lupus erythematous and rheumatoid arthritis, where autoantibodies lead to the development of chronic inflammation and loss of tissue function. MDSCs suppress T cells and other immune cells functions, but their ability to modulate B-cell responses is still poorly understood. The aim of this study is to study interactions between human polymorphonuclear-MDSCs (PMN-MDSCs) and B cells. For that purpose, we performed B-cell proliferation assays by co-culturing activated B-cell with PMNMDSCs. The data was then assessed by flow cytometry, image stream, and ELISA. Our studies demonstrate that human PMN-MDCs differentially modulate B-cell function by suppressing B-cell proliferation and antibody production in a stimulus- and dosedependent fashion. We further demonstrate that this MDSC-mediated effect is cellcontact dependent and involves established mediators such as arginase-1, nitric oxide (NO), reactive oxygen species (ROS) as well as B-cell death. Collectively, our studies provide novel evidence that human MDSCs modulate B cells, which could have future implications for immunotherapy approaches. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri de_DE
dc.rights.uri en
dc.subject.classification B-Lymphozyt de_DE
dc.subject.ddc 570 de_DE
dc.subject.other B cells en
dc.subject.other Myeloid-derived suppressor cells en
dc.subject.other MDSCs de_DE
dc.title Myeloid-derived suppressor cells regulate B-cell responses en
dc.type Dissertation de_DE
dcterms.dateAccepted 2017-02-02
utue.publikation.fachbereich Biologie de_DE
utue.publikation.fakultaet 7 Mathematisch-Naturwissenschaftliche Fakultät de_DE


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