Physiological relevance of TLR9 gene variants in human leukocyte

Čorbić, Irena (2010) Physiological relevance of TLR9 gene variants in human leukocyte. Diploma thesis, Faculty of Science > Department of Biology.

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Toll like receptor 9 (TLR9) is a sensor for unmethylated DNA stretches with CpG-motifs, usually presented in bacteria and viruses. TLR9 mediated signaling pathway leads to activation of innate immunity but also instructs the development of antigen-specific acquired immunity. In this study we examined the physiological relevance of previously found functional TLR9 gene variants, 111X and R892W, in human leukocyte. We investigated the effects of TLR agonists, CpG-ODN and R848 on the production of cytokines. Using ELISA, we measured the level of secreted IL-6 and IFNα in supernatants of cultivated plasmacytoid dendritic cells and IL-10 in supernatants of cultivated B cells. The results showed that mutations in TLR9 lead to reduced activation potential for IL-10 production in B cells. Using real time PCR (allelic discrimination assay) we investigated the frequency of the two TLR9 polymorphisms in the group of 550 patients suffering from different autoimmune diseases, and showed that these mutations are extremely rare, almost private. Finally, we screened family members for 111X mutation employing real time PCR method and found this mutation to be stably transmitted in the heterozygous form.

Item Type: Thesis (Diploma thesis)
Keywords: TLR9, gene variant, pDC, B cells, autoimmune disease
Supervisor: Matulić, Maja
Co-supervisor: Knežević, Jelena
Date: 2010
Number of Pages: 44
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 04 Sep 2014 12:04
Last Modified: 04 Sep 2014 12:04

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