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.
Regnase-1 is essential for B cell homeostasis to prevent immunopathology
Disclosures: C.F. Ware reported grants from NIH and grants from Perkins Foundation during the conduct of the study; and grants from E. Lilly Co., grants from Boehringer Ingelheim Co., personal fees from Coherus Inc, grants from Capella Biosciences, and personal fees from Capella Biosciences outside the submitted work. No other disclosures were reported.
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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. J Exp Med 3 May 2021; 218 (5): e20200971. doi: https://doi.org/10.1084/jem.20200971
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