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

Timsse Raj1, Arlinda Negraschus2, Vigo Heissmeyer1,2

  • 1Helmholtz Munich, Institute of Molecular Immune Regulation, Feodor-Lynen-Str. 21, 81377 Munich, Germany.

International Immunology
|December 16, 2022
PubMed

Insights

Roquin-1/2 and Regnase-1 RNA-binding proteins control inflammation to prevent autoimmune disease and enhance anti-tumor immunity. Modulating these proteins may improve cancer immunotherapies and dampen autoimmune reactions.

Area of Science:

  • Immunology
  • Molecular Biology
  • Gene Regulation

Background:

  • Roquin-1/2 and Regnase-1 are key RNA-binding proteins regulating pro-inflammatory mRNA.
  • Their dysregulation is linked to autoimmune diseases.
  • Inhibition of this pathway enhances anti-tumor CD8+ T cell responses.

Approach:

  • This review details the functions of Roquin-1/2 and Regnase-1.
  • It examines phenotypes associated with their genetic inactivation.
  • It discusses the reprogramming of T cell fates upon inducible inactivation.

Key Points:

  • Inactivating Roquin-1/2 and Regnase-1 reprograms CD4+ and CD8+ T cells.
  • Changes involve cell metabolism, activation, differentiation, and effector/memory decisions.
  • Precise modulation is crucial for therapeutic applications.

Conclusions:

  • Understanding Roquin-1/2/Regnase-1 regulation is vital for treating autoimmune diseases.
  • Targeting this system can boost efficacy of T cell-based cancer immunotherapies, including CAR T cells.
Keywords:
Regnase-1autoimmunityautoinflammationcancer therapypost-transcriptional gene regulation

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