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This thesis examines the evidence for regulatory ubiquitination by focusing on A20. It provides an insightful and in-depth evaluation of the current literature by critically examining the evidence of K63-linked regulatory ubiquitination in regulating cell-signalling. It is also the first thesis to directly test the role of regulatory ubiquitination in NF-kB signaling in vivo. The case for regulatory ubiquitination has been to a large extent predicated upon the presumed deubiquitinase activity of A20, long considered a key regulator of inflammatory responses as mice lacking A20 die from multi-organ inflammation and cachexia. The theses reports the creation and characterization of a knock-in m...
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It has been revealed that inflammation plays an important role in the progression of skin-related diseases, including burn or trauma wounds, diabetes wounds, pressure ulcers, radiation ulcers, keloids, hypertrophic scars, dermatitis, eczema, psoriasis, vitiligo, etc, causing skin tissue to exhibit over-inflammation, lower inflammation, or chronic inflammation. During this process, bacteria invasion, microbiota dysbiosis, or autoimmunity are known as the general initiators to induce the abnormal activity of immune cells and molecules and could change the crosstalk between immune cells and repair cells (or interstitial cells). Therefore, the research deep into the novel mechanisms of inflammation, the new signal pathway of immunity chain responses, or the new relationship between inflammation and repair cells, is of great interest for the design of novel therapies for skin-related diseases.
The skin is the human body's largest organ consisting of two layers: epidermis and dermis, and appendages: hair, and sweat glands. The skin not only wraps the body but also protects it from external stimuli and infection, perceives sensations such as pain and itch, and coordinates with various circulating immune cells for immune response/regulation. Recent studies have shown that inflammatory skin diseases, including psoriasis and atopic dermatitis, harbor systemic inflammation/immune abnormalities such as strong Th activation and expansion of specific immune cell subsets. Novel biologics and small molecule inhibitors targeting specific biomarkers and immune signals are much more effective and safer than conventional systemic therapies for these skin diseases.