Constitutively active STAT3 triggers the development of autoimmune myocarditis

Stat3 is a pleiotropic transcription factor displaying different functions. It is required for the differentiation of IL-17 secreting cells (Th17), which have been correlated with harmful inflammatory effects in autoimmune disorders. Thus Stat3 could be involved in the development and regulation of autoimmune diseases, but no model investigating Stat3 pathogenic functions in autoimmunity was so far available. We have recently generated knock/in mice expressing physiological levels of the constitutively active mutant form Stat3C (Stat3C/C mice). These mice develop a lethal form of autoimmune myocarditis, characterized by myeloid infiltration of the heart, production of anti-alpha myosin autoantibodies and high mRNA levels of proinflammatory cytokines. In addition, the development of Th17 cells appears to be enhanced by Stat3C expression as well as the circulating levels of the complement component C3. Thus, Stat3C/C mice appear to be a suitable model to study the role of chronically activated Stat3 in the development of autoimmunity. Further characterization of this model may lead to identify potential new strategies for therapeutic intervention in autoimmune diseases.