Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2017; 9(9): 152-158
Published online Sep 26, 2017. doi: 10.4252/wjsc.v9.i9.152
Role of aryl hydrocarbon receptor in mesenchymal stromal cell activation: A minireview
Danilo Candido de Almeida, Laura Sibele Martins Evangelista, Niels Olsen Saraiva Câmara
Danilo Candido de Almeida, Laura Sibele Martins Evangelista, Niels Olsen Saraiva Câmara, Department of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo, SP 04039-003, Brazil
Niels Olsen Saraiva Câmara, Department of Immunology, Institute of Biomedical Science, University of São Paulo, São Paulo, SP 05508-000, Brazil
Author contributions: de Almeida DC and Evangelista LSM wrote the manuscript; Câmara NOS contributed to extensive review and supervision.
Supported by São Paulo Research Public Foundation FAPESP and National Counsel of Technological and Scientific Development CNPq, No. 07/07193-3 and No. 12/02270-2.
Conflict-of-interest statement: The authors declare no potential conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Danilo Candido de Almeida, PhD, Affiliate Professor, Department of Medicine, Nephrology Division, Federal University of São Paulo, Rua Pedro de Toledo, 669 - 10 Andar - Frente, Vila Clementino, São Paulo, SP 04039-003, Brazil.
Telephone: +55-11-55764841
Received: March 29, 2017
Peer-review started: March 31, 2017
First decision: April 18, 2017
Revised: June 21, 2017
Accepted: July 7, 2017
Article in press: July 9, 2017
Published online: September 26, 2017

Mesenchymal stromal cells (MSCs) possess great therapeutic advantages due to their ability to produce a diverse array of trophic/growth factors related to cytoprotection and immunoregulation. MSC activation via specific receptors is a crucial event for these cells to exert their immunosuppressive response. The aryl-hydrocarbon receptor (AhR) is a sensitive molecule for external signals and it is expressed in MSCs and, upon positive activation, may potentially regulate the MSC-associated immunomodulatory function. Consequently, signalling pathways linked to AhR activation can elucidate some of the molecular cascades involved in MSC-mediated immunosuppression. In this minireview, we have noted some important findings concerning MSC regulation via AhR, highlighting that its activation is associated with improvement in migration and immunoregulation, as well as an increase in pro-regenerative potential. Thus, AhR-mediated MSC activation can contribute to new perspectives on MSC-based therapies, particularly those directed at immune-associated disorders.

Keywords: Mesenchymal stromal cells, Aryl-hydrocarbon receptor, Cell activation and immunosuppression

Core tip: The aryl-hydrocarbon receptor (AhR) is an endogenous sensor expressed in mesenchymal stromal cells (MSCs), regulating their immunomodulatory function. Therefore, in this review, we summarize important reports that demonstrate that AhR activation can substantially modulate the function of MSCs by mechanisms associated with: (1) The induction of the death signal in pro-inflammatory cells; (2) the suppression of pro-inflammatory genes/cytokines; (3) the improvement of migration and regenerative potential in acute inflammatory models; (4) the inhibition of mesodermal differentiation; and (5) the up-regulation of global immunosuppression. Thus, the influence of AhR activation on MSC function can establish new perspectives on MSC-based therapies, especially for immune-associated diseases.