Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2020; 12(7): 621-632
Published online Jul 26, 2020. doi: 10.4252/wjsc.v12.i7.621
Involvement of glycated albumin in adipose-derived-stem cell-mediated interleukin 17 secreting T helper cell activation
Julien Pestel, Maud Robert, Sara Corbin, Hubert Vidal, Assia Eljaafari
Julien Pestel, Maud Robert, Hubert Vidal, Assia Eljaafari, INSERM U1060 CarMen, Batiment CENS-ELI, Centre Hospitalier Lyon Sud, Pierre Bénite 69310, France
Julien Pestel, Maud Robert, Hubert Vidal, Assia Eljaafari, Faculty of Medicine, Université Claude Bernard Lyon 1, Batiment CENS-ELI, Centre Hospitalier Lyon Sud, Pierre Bénite 69310, France
Maud Robert, Department of Surgery in Gastro-enterology, Edouard Herriot Hospital, Lyon 69003, France
Sara Corbin, Public Health Department, Hospices Civils de Lyon, 1 quai des célestins Lyon 69002, France
Assia Eljaafari, DO-IT Research Team, Hospices Civils de Lyon, 1 quai des célestins, Lyon 69002, France
Author contributions: Pestel J performed the experiments, acquired and analyzed data and was involved in data interpretation and in the writing of the manuscript; Robert M provided the residual adipose tissues and participated in the writing of the manuscript; Corbin S supervised the statistical data and helped in the revision of the manuscript; Vidal H participated in the design of the study, data interpretation, and writing of the manuscript; Eljaafari A designed, coordinated the study, was involved in data interpretation and in the writing of the manuscript. All authors approved the final version of the article.
Institutional review board statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Committee for people Protection emanating from the Research Ministry, has given us its approval for the use of human adipose tissues isolated from residues of visceral surgery. Informed consents were signed by each donor.
Conflict-of-interest statement: No potential conflicts of interest were disclosed.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Assia Eljaafari, MD, PhD, Doctor, Senior Scientist, CarMeN Laboratory, INSERM U1060, University Claude Bernard Lyon 1 and Hospices Civils de Lyon, Batiment CENS-ELI, Centre Hospitalier Lyon Sud, 165 chemin du Grand Revoyet, Pierre Bénite 69310, France.
Received: February 28, 2020
Peer-review started: February 28, 2020
First decision: April 18, 2020
Revised: May 19, 2020
Accepted: June 10, 2020
Article in press: June 10, 2020
Published online: July 26, 2020
Research background

Advanced glycation end products (AGE) are involved in type 1 diabetes (T1D) through reduction of glucose uptake and attenuation of insulin sensitivity. Moreover, AGE are known to promote interleukin (IL)-17A secreting T cells.

Research motivation

Adipose Tissue (AT), and especially pancreatic AT is a pathogenic factor leading to beta cell destruction partly due to IL-17A secreting T helper (Th17) cell recruitment; IL-17A/F are pro-inflammatory cytokines known to play an important role in AT-low grade inflammation and propagation of inflammation outside AT.

Research objectives

We have previously shown that adipose-derived stem cells (ASC) promote Th17 cells in obese AT, but not or less in lean AT. Here, we investigated whether AGE could improve lean ASC ability to promote IL-17A production by T cells.

Research methods

With this aim, we cocultured ASC from lean AT with mononuclear cells in the presence of glycated human serum albumin (G-HSA) or human serum albumin. We then analyzed the influence of AGE by blocking their ability to bind to receptor of advanced glycated end products (RAGE). IL-17A and other pro-inflammatory cytokine secretions were measured, together with surface expression of RAGE, and other relevant molecules.

Research results

We have demonstrated herein that G-HSA enhances IL-17A, interferon gamma and tumor necrosis factor alpha secretion by MNC in the presence of ASC harvested from lean individuals. This effect involves the RAGE/AGE axis as assessed by anti-RAGE blocking monoclonal antibodies (mAb) and is associated with increased expression of RAGE and human leukocyte antigen-DR molecules.

Research conclusions

Thus, our results demonstrate that G-HSA is able to improve lean ASC-mediated IL-17A production in AT, suggesting a new mechanism by which AGE could contribute to T1D pathophysiology.

Research perspectives

Here we propose a mechanism by which AT can lead to the recruitment of Th17 cells in lean individuals through activation of the AGE/RAGE axis. Because pancreatic fat has been involved in the pathogenicity of T1D, this model deserves to be validated in animal studies, in order to evaluate the efficacy of RAGE blocking mAb as a therapeutic tool.