RESUMO
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.
Assuntos
Autoimunidade/genética , Linfócitos B/metabolismo , Homeostase/genética , Ativação Linfocitária/genética , Ribonucleases/genética , Animais , Diferenciação Celular/genética , Perfilação da Expressão Gênica/métodos , Camundongos Knockout , Camundongos Transgênicos , RNA-Seq/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Ribonucleases/metabolismoRESUMO
[reaction: see text] Lewis acid mediated addition of chiral titanium enolates to glycals provides either alpha- or beta-1'-methyl-substituted C-glycosides. This highly stereoselective methodology permits the modular preparation of three of the four possible diastereomers.
