IL-4 in Autoimmune Flaky Skin Mice

<p>Flaky skin mutant (Ttc7fsn) mice display systemic immune dysfunction including splenomegaly, glomerulonephritis, elevated levels of serum IgE, a substantial increase in the number of splenic B cells and a dramatic increase in IL-4 production. Previous work indicated constitutively activated Stat6 in splenic B cells; herein we have demonstrated this to be the result of continuous IL-4 signaling as nuclear localization studies suggested B cells have the ability to turn over activated Stat6 ex vivo when the IL-4 signal is removed. In addition, actinomycin D studies provide evidence for an increase in IL-4 mRNA stability which leads to dramatically increased IL-4 protein production resulting in a driving force toward systemic autoimmunity. Although the function of the Ttc7fsn gene is as yet unknown, we suggest that it may lead to a greater understanding of the mechanisms involved in IL-4 regulation.