Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation

Abstract The introduction of the CTLA-4 recombinant fusion protein has demonstrated therapeutic effects by selectively modulating T-cell activation in rheumatoid arthritis. Here we show, using a forward genetic approach, that mutation SH3gl1 gene encoding endocytic Endophilin A2 is associated with development arthritis rodents. Defective expression affects T cell effector functions and alters threshold autoreactive cells, thereby leading to complete protection from chronic autoimmune inflammatory disease both mice rats. We further show SH3GL1 regulates human signaling receptor internalization, its upregulated patients. Collectively our data identify as key regulator activation, potential target for treatment diseases.