Open AccessRegnase-1 is essential for B cell homeostasis to prevent immunopathology
Author(s) -
Numana Bhat,
Richard Virgen-Slane,
Parham Ramezani-Rad,
Charlotte R Leung,
Cindi Chen,
Daniel Balsells,
Ashima Shukla,
Elaine Kao,
John Apgar,
Mingui Fu,
Carl F. Ware,
Robert C. Rickert
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20200971
Subject(s) - immune system , regulator , autoimmunity , microbiology and biotechnology , biology , b cell , t cell , immunology , homeostasis , cell , immunopathology , gene , genetics , antibody
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.