creators_name: Tiwari, Drishti
creators_name: Ahuja, Nancy
creators_name: Kumar, Sumit
creators_name: Kalra, Rashi
creators_name: Nanduri, Ravikanth
creators_name: Gupta, Shalini
creators_name: Khare, Asheesh K
creators_name: Bhagyaraj, Ella
creators_name: Arora, Rashmi
creators_name: Gupta, Pawan
type: article
datestamp: 2022-07-25 09:09:20
lastmod: 2022-07-25 09:09:20
metadata_visibility: show
title: Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation
ispublished: pub
subjects: QR
keywords: Asthma; GATA3; Nuclear receptor; T lymphocytes; T-bet
note: The copyright of this article belongs to Springer 
abstract: 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.
date: 2022-05-21
date_type: published
publication: Cellular and Molecular Life Sciences
volume: 79
number: 6
publisher: Springer 
refereed: TRUE
official_url: https://link.springer.com/article/10.1007/s00018-022-04323-0
citation:   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).