Published online Jul 26, 2020. doi: 10.4252/wjsc.v12.i7.621
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
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.
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.
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.
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.
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.
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.
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.