Roquin-dependent gene regulation in immune-mediated diseases and future therapies
Timsse Raj, Arlinda Negraschus, Vigo Heissmeyer
Abstract
The RNA-binding proteins Roquin-1/2 and Regnase-1 exert essential regulation by controlling pro-inflammatory mRNA expression to prevent autoimmune disease. More recently, inhibition of this post-transcriptional gene regulatory program has been demonstrated to enable enhanced anti-tumor responses by tumor antigen-specific CD8+ T cells. In this review, we describe the functions of these RNA-binding proteins and the phenotypes that arise in association with genetic inhibition or inactivation. We discuss how inducible inactivation of the system reprograms CD4+ and CD8+ T cell fates by changing cell metabolism, activation, differentiation or effector/memory decisions. We furthermore outline what we need to know to precisely modulate this system in order to dampen autoimmune reactions or boost the efficacy of adoptively transferred T cells or chimeric antigen receptor (CAR) T cells in cancer immunotherapies.