TY  - JOUR
N1  - The copyright of this article belongs to Springer 
ID  - open2998
UR  - https://link.springer.com/article/10.1007/s00018-022-04323-0
IS  - 6
A1  - Tiwari, Drishti
A1  - Ahuja, Nancy
A1  - Kumar, Sumit
A1  - Kalra, Rashi
A1  - Nanduri, Ravikanth
A1  - Gupta, Shalini
A1  - Khare, Asheesh K
A1  - Bhagyaraj, Ella
A1  - Arora, Rashmi
A1  - Gupta, Pawan
Y1  - 2022/05/21/
N2  - Nuclear receptors are a unique family of transcription factors that play cardinal roles in physiology and plethora of human diseases. The adopted orphan nuclear receptor Nr1d1 is a constitutive transcriptional repressor known to modulate several biological processes. In this study, we found that Nr1d1 plays a decisive role in T helper (Th)-cell polarization and transcriptionally impedes the formation of Th2 cells by directly binding to the promoter region of GATA binding protein 3 (GATA3) gene. Nr1d1 interacts with its cellular companion, the nuclear receptor corepressor and histone deacetylase 3 to form a stable repression complex on the GATA3 promoter. The presence of Nr1d1 also imparts protection against associated inflammatory responses in murine model of asthma and its ligand SR9011 eased disease severity by suppressing Th2 responses. Moreover, Chip-seq profiling uncovered Nr1d1 interactions with other gene subsets that impedes Th2-linked pathways and regulates metabolism, immunity and brain functions, therefore, providing empirical evidence regarding the genetic link between asthma and other comorbid conditions. Thus, Nr1d1 emerges as a molecular switch that could be targeted to subdue asthma.
PB  - Springer 
JF  - Cellular and Molecular Life Sciences
VL  - 79
KW  - Asthma; GATA3; Nuclear receptor; T lymphocytes; T-bet
TI  - Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation
ER  -