AUTHOR=Hams Emily , Roberts Joseph , Bermingham Rachel , Fallon Padraic G. 

TITLE=Functions for Retinoic Acid-Related Orphan Receptor Alpha (RORα) in the Activation of Macrophages During Lipopolysaccharide-Induced Septic Shock

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.647329

DOI=10.3389/fimmu.2021.647329

ISSN=1664-3224

ABSTRACT=The transcription factor ROR plays an important role in regulating circadian rhythm, inflammation, metabolism and cellular development. Herein we show that in the absence of functional ROR in mice there is reduced susceptibility to LPS-induced endotoxic shock, with selective decreases in release of  pro-inflammatory cytokines.  Treatment of mice with a  ROR selective synthetic inhibitor also reduced the severity of LPS-induced endotoxemia. The reduction in responses in Rora deficient mice was associated with an alterations in metabolic and pro-inflammatory functions of macrophages, both in vivo peritoneal macrophages and in vitro generated bone marrow derived macrophages. Using LysMCreRorafl/sg mice the reduced susceptibility to LPS was shown to be specific to Rora expression in the macrophages. This study identifies that Rora-mediated regulation of macrophages impacts on the pro-inflammatory responses elicited by LPS.