National Repository of Grey Literature 5 records found  Search took 0.00 seconds. 
The role of the immune system in the immunopathogenesis of autoimmune diseases and the therapeutic modulation of autoimmune reaction by tolerogenic dendritic cells
Dáňová, Klára ; Palová Jelínková, Lenka (advisor) ; Prokešová, Ludmila (referee) ; Heneberg, Petr (referee)
Immunotherapy based on dendritic cells (DCs) was first tested in clinical trials for the treatment of cancer in the 1990s. Currently, the ability of DCs to modulate immune responses is also being tested in several clinical studies focusing on autoimmune disease treatment with the aim of suppressing the overactivated immune system and restoring immune tolerance. For this purpose, so-called tolerogenic DCs with considerable suppressive potential are used. Tolerogenic DCs can be generated ex vivo from monocytes using pharmacological agents, which in DCs induce a regulatory phenotype with low expression of activation markers, high expression of inhibitory markers and secretion of suppressive cytokines. In the first part of this study, we show that cultivation of human blood monocytes in the presence of glucocorticoid dexamethasone and 19- nor-1,25-dihydroxyvitamin D2 (paricalcitol) enables ex vivo generation of tolerogenic DCs with a highly stable suppressive phenotype characterized by upregulated IL-10 production, inhibitory IL- T3 and PD-L1 molecule expression, the low stimulatory capacity and the ability to induce regulatory T cell development. Moreover, we show that metabolic changes and signaling through NF-κB, p38 MAPK, ERK1/2 molecules and the mTOR/STAT3 pathway play an important role in the...
New aspects of the cell submembrane signaling
Heneberg, Petr ; Dráber, Petr (advisor) ; Bilej, Martin (referee) ; Folk, Petr (referee)
This dissertation contributes to elucidation of some mechanisms of the mammalian cell submembrane signaling. Major part of the research was conducted on mast cells and basophils activated via the high affinity IgE receptor, FcεRI, or via the cell surface glycoprotein Thy-1. New roles of actin cytoskeleton in mast cell signaling via FcεRI and Thy-1 are described. Discovery of new transmembrane adaptor protein non-T cell activation linker, NTAL, short time before the initiation of work on the thesis led to the increased attention paid to this protein. Dramatic changes of signaling in mast cells deficient in NTAL, or with up- or down-regulated expression of this protein are described. NTAL was also found to be one of proteins phosphorylated following the Thy-1 aggregation. Spatiotemporal distribution of surface glycoprotein Thy-1 at different levels of resolution and some biochemical properties of cells activated via Thy-1 are depicted. Screen for nonreceptor hitherto unknown protein tyrosine phosphatases in mast cells and basophils was conducted and initial analysis of spatiotemporal distribution and function of phosphatase PTP20 in mast cell signaling was performed. Next, the role of reactive oxygen and nitrogen species in the regulation of mast cell protein tyrosine phosphatases was summarized. New...

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