Please use this identifier to cite or link to this item:
Title: Chloroquine modulates inflammatory autoimmune responses through Nurr1 in autoimmune diseases
Authors: Park, Tae-Yoon
Jang, Yongwoo
Kim, Woori
Shin, Joon
Toh, Hui Ting
Kim, Chun-Hyung
Yoon, Ho Sup
Leblanc, Pierre
Kim, Kwang-Soo
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Park, T.-Y., Jang, Y., Kim, W., Shin, J., Toh, H. T., Kim, C.-H., . . . Kim, K.-S. (2019). Chloroquine modulates inflammatory autoimmune responses through Nurr1 in autoimmune diseases. Scientific Reports, 9(1), 15559-. doi:10.1038/s41598-019-52085-w
Journal: Scientific Reports 
Abstract: For over a half-century the anti-malarial drug chloroquine (CQ) has been used as a therapeutic agent, alone or in combination, to treat autoimmune diseases. However, neither the underlying mechanism(s) of action nor their molecular target(s) are well defined. The orphan nuclear receptor Nurr1 (also known as NR4A2) is an essential transcription factor affecting the development and maintenance of midbrain dopaminergic neurons. In this study, using in vitro T cell differentiation models, we demonstrate that CQ activates TREG cell differentiation and induces Foxp3 gene expression in a Nurr1-dependent manner. Remarkably, CQ appears to induce Nurr1 function by two distinct mechanisms: firstly, by direct binding to Nurr1's ligand-binding domain and promoting its transcriptional activity and secondly by upregulation of Nurr1 expression through the CREB signaling pathway. In contrast, CQ suppressed gene expression and differentiation of pathogenic TH17 cells. Importantly, using a valid animal model of inflammatory bowel disease (IBD), we demonstrated that CQ promotes Foxp3 expression and differentiation of TREG cells in a Nurr1-dependent manner, leading to significant improvement of IBD-related symptoms. Taken together, these data suggest that CQ ameliorates autoimmune diseases via regulating Nurr1 function/expression and that Nurr1 is a promising target for developing effective therapeutics of human inflammatory autoimmune diseases.
ISSN: 2045-2322
DOI: 10.1038/s41598-019-52085-w
Rights: © 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

Citations 20

Updated on Mar 29, 2023

Web of ScienceTM
Citations 20

Updated on Mar 28, 2023

Page view(s)

Updated on Mar 29, 2023

Download(s) 50

Updated on Mar 29, 2023

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.