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• W194213778 endingPage "76" @default.
• W194213778 startingPage "1" @default.
• W194213778 abstract "The innate immune system relies on several pattern recognition receptors (PRRs) to identifypathogen associated molecular patterns (PAMPs). One of the most prominent non-clonal, germlineencoded but yet not fully characterized PRR group are the NOD-like receptors (NLRs). Here I aimto characterize a hitherto rarely described member of the NLRs named NOD-like receptor CARDdomain containing 3 (NLRC3). Recent studies indicated, that NLRC3 is a cytosolic receptor whichnegatively regulates T cell function.This thesis utilizes several experimental approaches to access the cellular localization of NLRC3,its functional interactions, and role in inflamed tissue. Microscopical studies showed, that NLRC3is localized in the cytoplasm. Analysis of different organs indicated, that NLRC3 transcript levelare elevated in immune relevant tissues, but not in the intestinal tract. A Y2H screen indicated a potentialinteraction with the mitochondrial protein IMMT/Mitofilin. Although a direct interactionremained elusive, NLRC was detected in close spatial proximity of mitochondria via immunefluorescenceand identified in mitochondrial lysates. NLRC3 was found to interfere with NFBsignaling in a dose dependent manner. Dual luciferase assays were performed revealing connectionsto TRAF6 and ERSE. NLRC3 seems to negatively regulate the TRAF6 mediated NFBresponse. In combination with a potent stressor, such as tunicamycin elevates NLRC3 the ERSEpromoter activity. This reaction connects NLRC3 to cellular mechanisms of the unfolded proteinresponse, and subsequently to mitochondrial stress reactions. NLRC3 was found to be downregulatedin biopsies of WG patients. During this thesis Nlrc3+/+ and Nlrc3-/- mice were bred and utilizedin several experiments. Cytokine level in bone marrow derived macrophages varied betweenNlrc3+/+ and Nlrc3-/- in response to LPS stimulation. A DSS induced colitis was conducted andrevealed, that NLRC3 seems to be beneficial for survival and disease severity. These experimentssignificantly enlarged the knowledge about NLRC3, pointing at the protective role of NLRC3during cellular stress response and inflammation. NLRC3 is an important regulator in immunemodulation." @default.
• W194213778 created "2016-06-24" @default.
• W194213778 creator A5071723433 @default.
• W194213778 date "2014-06-04" @default.
• W194213778 modified "2023-09-27" @default.
• W194213778 title "Functional characterization of NLRC3" @default.
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