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Roquin-dependent gene regulation in immune-mediated diseases and future therapies.

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The RNA-binding proteins Roquin-1/2 and Regnase-1 exert essential regulation by controlling proinflammatory mRNA expression to prevent autoimmune disease. More recently, inhibition of this post-transcriptional gene regulatory program has been demonstrated… Click to show full abstract

The RNA-binding proteins Roquin-1/2 and Regnase-1 exert essential regulation by controlling proinflammatory 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.

Keywords: gene regulation; regulation; gene; regulation immune; roquin dependent; dependent gene

Journal Title: International immunology
Year Published: 2022

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