Regnase-1 is essential for B cell homeostasis to prevent immunopathology.

Numana Bhat, Richard Virgen-Slane, Parham Ramezani-Rad, Charlotte R Leung, Cindi Chen, Daniel Balsells, Ashima Shukla, Elaine Kao, John R Apgar, Mingui Fu, Carl F Ware, Robert C Rickert

The Journal of experimental medicine 2021 May 03

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Regnase-1 is an emerging regulator of immune responses with essential roles in the posttranscriptional control of immune cell activation. Regnase-1 is expressed in B cells; however, its B cell-specific functions remain unknown. Here, we demonstrate that Regnase-1 prevents severe autoimmune pathology and show its essential role in maintaining B cell homeostasis. Using Cre driver mice for ablation of Regnase-1 at various stages of B cell development, we demonstrate that loss of Regnase-1 leads to aberrant B cell activation and differentiation, resulting in systemic autoimmunity and early morbidity. The basis of these findings was informed by gene expression data revealing a regulatory role for Regnase-1 in the suppression of a transcriptional program that promotes B cell activation, survival, and differentiation. Overall, our study shows that Regnase-1 exerts critical control of B cell activation, which is required for prevention of immunopathology. © 2021 Bhat et al.

Citation

Numana Bhat, Richard Virgen-Slane, Parham Ramezani-Rad, Charlotte R Leung, Cindi Chen, Daniel Balsells, Ashima Shukla, Elaine Kao, John R Apgar, Mingui Fu, Carl F Ware, Robert C Rickert. Regnase-1 is essential for B cell homeostasis to prevent immunopathology. The Journal of experimental medicine. 2021 May 03;218(5)