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

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation
 
Creator Tiwari, Drishti
Ahuja, Nancy
Kumar, Sumit
Kalra, Rashi
Nanduri, Ravikanth
Gupta, Shalini
Khare, Asheesh K
Bhagyaraj, Ella
Arora, Rashmi
Gupta, Pawan
 
Subject QR Microbiology
 
Description 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.
 
Publisher Springer
 
Date 2022-05-21
 
Type Article
PeerReviewed
 
Relation https://link.springer.com/article/10.1007/s00018-022-04323-0
http://crdd.osdd.net/open/2998/
 
Identifier Tiwari, Drishti and Ahuja, Nancy and Kumar, Sumit and Kalra, Rashi and Nanduri, Ravikanth and Gupta, Shalini and Khare, Asheesh K and Bhagyaraj, Ella and Arora, Rashmi and Gupta, Pawan (2022) Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation. Cellular and Molecular Life Sciences, 79 (6).