In the case of scleroderma, for example, agonization of TLR4 was shown to drive a cycle of fibrosis, leading to further FNIII EDA-containing FN expression, increasing TLR4 agonization and promoting continued fibrosis15; as such, TLR4 agonization via FNIII EDA is central to the pathophysiology of the disease. This evidence concerns the gene TLR4 and scleroderma.