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Different capacity of in vitro generated monocyte-derived dendritic cells of newborns of healthy and allergic mothers to prime immune responses
Súkeníková, Lenka ; Hrdý, Jiří (advisor) ; Javorková, Eliška (referee)
(EN) Reduced microbial stimulation of an immature neonatal immune system can lead to a poor balance adjustment of immune responses, thus contributing to the development of allergic diseases, whose incidence continues to rise. One of the promising precautionary measures seems to be an early preventive administration of probiotic bacteria to pregnant or nursing mothers, or to newborns. Previous works have described a beneficial effect of Escherichia coli O83:K24:H31 (E. coli O83) in the prevention of allergic diseases. In order to contribute to the clarification of E. coli O83 effects on the neonatal immune system, its immune- modulating properties were tested in vitro on umbilical cord blood cells. The ability of E. coli O83 to support the maturation of in vitro-derived dendritic cells from cord blood precursors (moDCs) of the children of healthy (children with a relatively low risk of allergy) and allergic (children at a relatively high risk of developing allergies) mothers was tracked by flow cytometry, qPCR and ELISA. Probiotic bacteria-stimulated moDCs were subsequently cultured with autologous naive CD4+ T lymphocytes and immune response polarization was also characterised by flow cytometry, qPCR, and ELISA. It was evident from the results that E. coli O83 promoted moDCs maturation. The presence of...
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Emerging role of Toll-like receptors in central tolerance
Súkeníková, Lenka ; Filipp, Dominik (advisor) ; Černý, Jan (referee)
Medullary thymic epithelial cells (mTECs) provide a specific thymic microenvironment for the processes associated with T cell development. Their irreplaceable function is the expression of specific set of antigens which are expressed only in peripheral tissues, called tissue restricted antigens (TRAs). Such expression, often referred to as promiscuous, was originally described with the discovery of transcriptional regulator Aire. Aire, which has a potential to interact with many other transcription factors, also binds to DNA, and thus can alter the general pattern of cellular gene expression. T cells exhibiting a strong affinity to TRAs expressed on mTECs are removed from the thymus by negative selection or their development is deviated to regulatory T cell (Treg) lineage. Studies on mice and humans confirmed the critical role of Aire protein in the establishment of the central tolerance. Inactivating mutations in Aire gene cause deficiency in TRA expression, failure to remove and the escape of self-specific T cells from the thymus to periphery, and in turn, autoimmunity. Experimental evidence points to the key role of NF-κB signaling pathway in mTECs development. The very same pathway is regulated also by Toll-like receptors (TLRs), which recognize evolutionary conserved structures derived from...
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