The transcription factor Ets1 cooperates with IL-17 signaling to promote both autoimmunity and immunodeficiency.

Ets1 is a transcription factor present in B and T lymphocytes, that has an important role in regulating the immune response. Mice that are lacking Ets1 (Ets1 KO) develop spontaneous autoimmune disease and increased levels of the cytokine IL-17. Since IL-17 has also found to be elevated in other autoimmune, it has been proposed that IL-17 drives the pathogenesis of autoimmune disease. In order to test this model, our lab has created a mouse that is lacking both Ets1 and the receptor for IL-17. To our surprise, mice that lacked both Ets1 and the receptor for IL -17 (double knockout mice) developed worse symptoms of autoimmune disease instead of less. Another unexpected finding was that double knockout mice also present with an increased susceptibility to the pathogen Staphylococcus aureus (S. aureus). The focus of my research therefore is figuring out the mechanisms that connects autoimmune disease with immunodeficiency.

Lee Ann Garrett-Sinha, PhD