creators_name: Chandra, Vemika
creators_name: Bhagyaraj, Ella
creators_name: Nanduri, Ravikanth
creators_name: Ahuja, Nancy
creators_name: Gupta, Pawan
type: article
datestamp: 2016-02-01 04:29:56
lastmod: 2016-02-01 04:29:56
metadata_visibility: show
title: NR1D1 ameliorates Mycobacterium tuberculosis clearance through regulation of autophagy.
ispublished: pub
subjects: QR
keywords: Mycobacterium tuberculosis; autophagy; gene regulation; nuclear receptors; transcription factors
note: Copyright of this article belongs to Taylor and Francis.
abstract: NR1D1 (nuclear receptor subfamily 1, group D, member 1), an adopted orphan nuclear receptor, is widely known to orchestrate the expression of genes involved in various biological processes such as adipogenesis, skeletal muscle differentiation, and lipid and glucose metabolism. Emerging evidence suggests that various members of the nuclear receptor superfamily perform a decisive role in the modulation of autophagy. Recently, NR1D1 has been implicated in augmenting the antimycobacterial properties of macrophages and providing protection against Mycobacterium tuberculosis infection by downregulating the expression of the IL10 gene in human macrophages. This antiinfective property of NR1D1 suggests the need for an improved understanding of its role in other host-associated antimycobacterial pathways. The results presented here demonstrate that in human macrophages either ectopic expression of NR1D1 or treatment with its agonist, GSK4112, enhanced the number of acidic vacuoles as well as the level of MAP1LC3-II, a signature molecule for determination of autophagy progression, in a concentration- and time-dependent manner. Conversely, a decrease in NR1D1 in knockdown cells resulted in the reduced expression of lysosomal-associated membrane protein 1, LAMP1, commensurate with a decrease in the level of transcription factor EB, TFEB. This is indicative of that NR1D1 may have a regulatory role in lysosome biogenesis. NR1D1 being a repressor, its positive regulation on LAMP1 and TFEB is suggestive of an indirect byzantine mechanism of action. Its role in the modulation of autophagy and lysosome biogenesis together with its ability to repress IL10 gene expression supports the theory that NR1D1 has a pivotal antimycobacterial function in human macrophages.
date: 2015-11-02
date_type: published
publication: Autophagy
volume: 11
number: 11
publisher: Taylor & Francis
pagerange: 1987-1997
refereed: TRUE
issn: 1554-8635
official_url: http://www.tandfonline.com/doi/abs/10.1080/15548627.2015.1091140?journalCode=kaup20
citation:   Chandra, Vemika and Bhagyaraj, Ella and Nanduri, Ravikanth and Ahuja, Nancy and Gupta, Pawan  (2015) NR1D1 ameliorates Mycobacterium tuberculosis clearance through regulation of autophagy.  Autophagy, 11 (11).  pp. 1987-1997.  ISSN 1554-8635