The influence of lymphotoxin-driven chronic inflammation on tissue homeostasis and carcinogenesis

In my thesis I investigated the contribution of lymphotoxin mediated signaling to the pathology of chronic inflammatory diseases of the urinary tract and the skeletal muscle. I could show that lymphotoxin induced a positive feedforward loop leading to cytokine and chemokine production by kidney cells thereby further aggravating inflammatory pathology. By generation of a transgenic mouse model I could study the role of lymphotoxin in chronic skeletal muscle inflammation. Tissue specific overexpression of lymphotoxin in skeletal muscle induced strong inflammation and a similar pathology as found in human myositis patients. Furthermore, I generated a model of chronic cystitis by bladder specific overexpression of lymphotoxin. Hence, we are now able to investigate the role of lymphotoxin mediated signaling in bladder carcinogenesis.