The MRTFs are required for thymocyte trafficking and T _reg -mediated immune tolerance

The MRTFs (myocardin-related transcription factors) are essential for effective cytoskeletal function during differentiation and development. To investigate the role played by the MRTFs in T cell development and function we inactivated Mrtfb in Mrtfa -null mice at the DN2 stage ( Mrtfab KO ^T animals). Positive selection, and development of Mrtfab KO ^T regulatory (T _reg ), γδ, and NK T cells proceeded normally. Thymic egress was impaired, however, with mature T cells accumulating at the cortico-medullary junction, and in vitro Mrtfab KO ^T thymocytes exhibited impaired cytoskeletal responses to S1P and migratory cytokines. Mrtfab KO ^T mice were lymphopenic, with defective homeostatic proliferation and T cell homing to peripheral lymphoid organs. Although thymocyte negative selection was unaffected, Mrtfab KO ^T animals develop autoimmune phenotypes in lacrimal gland and intestinal mucosa. Using the experimental colitis model, we show that these phenotypes reflect functional deficits in Mrtfab KO ^T T _reg cells. Our findings show that MRTF-SRF signalling plays an unanticipated role in thymocyte egress and immune tolerance, and reveal a role of the MRTFs in T _reg function.