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Regulation of IL-17 receptor complex signaling.
Šemberová, Tereza ; Dráber, Peter (advisor) ; Truksa, Jaroslav (referee)
Inflammatory immune response is essential for maintaining the defense against invading pathogens, although its aberrant activation leads to impaired self tolerance and development of autoimmune pathologies. Interleukin-17A (also known as IL-17), is a major proinflammatory cytokine, which contributes to the development and maintenance of inflammation and provides protection against several bacterial and yeast infections. However, extreme activation of IL-17 signaling leads to autoimmune pathologies. Thus, a strict regulation of IL-17 signal transduction is crucial to prevent progression of autoimmunity. Non-degradative ubiquitination is one of the main mechanisms regulating IL-17 signaling. Main E3 ubiquitin ligase within this signal transduction is TRAF6, which is also participating in several signaling pathways within the immune system. Non-degradative polyubiquitin chains created within inflammatory signaling complexes recruit signaling proteins such as IKK complex and TAK1 kinase, crucial for triggering of NF-κB and MAPKs downstream pathways. However, activation of these pathways upon IL-17 is very weak in comparison with other inflammatory stimuli, indicating a presence of a strong negative feedback loop. In this thesis, we establish the role of several regulatory molecules in IL-17 signaling....
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