Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation

Chronic HDM exposure shows time-of-day and sex-based differences in inflammatory response associated with lung circadian clock disruption

“…Rev-erbα KO shows elevated Th2 cells and related cytokines indicating the protective role of NR1D1 in allergic asthma. 40 Results from our study support the possible role of Nr1d1/2 (reduced mRNA expression) in chronic HDM-induced allergic asthma with heightened il4 , il5 , and il13 expression at ZT12. However, we believe that altered clock genes in the lungs during asthma are a result of complex molecular interaction between transcriptional-translational regulation of circadian clock molecules (at the mRNA and protein level) and other key transcription factors which needs further investigation.…”

Melatonin regulates circadian clock proteins expression in allergic airway inflammation

“…Studies have emphasized the importance of clock genes including Bmal1, Clock, Per1, Per2, Per3, Cry1, Cry2, Timeless and etc in the pathophysiological process of asthma. For example, Bmal1 has been reported to regulate asthma airway phenotypes [ 28 , 29 ], while REV-ERBα/Nr1d1 has been found to gate HDM-induced airway hyperresponsiveness [ 9 , 30 ] probably by regulating the polarization of T helper cells and differentiation [ 31 ]. Disruption of clock contributes to epithelial barrier dysfunction and deregulated immune responses to promote asthma [ 13 ].…”

Targeting NR1D1 in organ injury: challenges and prospects

“…The principal transcription factor for Th2 cell differentiation is GATA binding protein 3 (GATA3) [ 43 ]. NR1D1 directly binds to the Gata3 promoter and interacts with its cellular companion NCOR-HDAC3 to create a durable repression complex, ultimately restricting Th2 cell production [ 44 ]. Retinoic acid-related orphan receptor γt (RORγt) is the master transcription factor for the differentiation of interleukin-17-producing CD4 Th17 cells, which are a class of proinflammatory immune cells that protect mucosal surfaces from bacterial and fungal infections [ 45 , 46 ].…”