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Immunogenetic studies on autoimmune diabetes mellitus
Kološtová, Katarína ; Černá, Marie (advisor) ; Mateička, František (referee) ; Štechová, Kateřina (referee)
Immunogenetic studies on autoimmune diabetes. Aims of the study: The study has to characterize the genetic background of patients with different types of diabetes mellitus (T1D in children, T1D in adults, LADA, T2D, MODY). The relationship of the diabetes associated HLA-DRB1*04 and NFKB1 genes to the disease course was proved further in the functional studies of the mRNA gene expression. Patients were divided into the tested subgroups in relation to the HLA class II, NFKB1, and NFKBIA genotypes and disease type (T1DM in children, T1DM in adults, and LADA). Results and Conclusion: According to our findings we can conclude that the progression of the diabetes in T1D adults, T1D children and LADA is strongly influenced by different immunogenetic background modifying the ethiopathogenesis of diabetes in the above described groups. Our results offer new possibilities for the population risk testing and may be that far used in the future for better diagnostics of the diabetic's adults.
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Th17 lymphocytes and autoimmunity diseases with the intention of diabetes 1. type
Labiková, Jana ; Procházková, Jana (referee) ; Štechová, Kateřina (advisor)
Th17 cells were recently identified as a cell source of IL-17. They turned up to be a T cell lineage independent of previously described Th1 and Th2. The differentiation of naive CD4+ T cells towards Th17 requires the combination of TGFβ (a cytokine essential for the development of anti-inflammatory regulatory T cells) plus IL-6 or IL-21. IL-23 is required for in vivo function and phenotype maintenance of Th17. STAT3 and RORγt were identified as pivotal transcription factors in Th17 differentiation program. Th17 proved to have pro- inflammatory effects and are characterized by the production of IL-17A, IL-17F and IL-22 - cytokines implicated in host defense against certain extracellular pathogens. The cytokine products of Th17 cells act on wide range of cell types. They induce cytokines, chemokines and metalloproteinases and they also mediate neutrophil recruitment and production of antimicrobial peptides. Autoreactive Th17 are highly pathogenic and the production of IL-17 has been detected in several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis, Crohn's disease and type 1 diabetes. These diseases were thought to be mediated by Th1 cells, but it is becoming increasingly clear that the regulation of autoimmunity is influenced at least in some diseases by Th17 cells as well.
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