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Novel protocols to induce tolerance to solid organ transplants
Chakhtoura, Marita
Chakhtoura, Marita
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Thesis/Dissertation
Date
2016
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Microbiology and Immunology
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http://dx.doi.org/10.34944/dspace/916
Abstract
Dendritic cells (DCs) are the sentinels of the immune system. They mature at the encounter of the appropriate stimuli or danger signals, which induce them to perform pro-inflammatory antigen presentation to naïve and memory T cells, resulting in inflammation. Remaining in an immature state however, DCs acquire a tolerogenic phenotype. When activated by TLR ligands, DCs undergo metabolic re-programming and switch to TBK1/IKKe/AKT-induced glycolysis at the early activation phase, which is sustained due to nitric oxide (NO)-mediated inhibition of mitochondrial metabolism at the later activation phase. Targeting DC activation in the view of promoting less activated or tolerogenic DCs could be an approach to reduce or abrogate inflammation in settings such as solid organ transplant rejection or in autoimmune diseases such as systemic lupus erythematosus (SLE). In this thesis, we present data pertaining to three different approaches for targeting DC activation including 1) the use of ethyl p
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