Abstract
Background Early stages of diabetic nephropathy (DN) are characterized by an influx of inflammatory cells. Interactions between infiltrating T cells and podocytes may play an important role in the ongoing inflammatory response and remodelling. The aim of this study was to explore the role of IL-17 and CD40 ligand (CD40L) in DN. Methods The study design involved a case series. Kidney biopsy samples of 69 patients with type 2 diabetes were assessed for the presence of CD4 + IL-17 + T cells. The number of CD4 + IL-17 + T cells were counted and correlated with clinical and laboratory findings. Additionally, advanced glycation end-products (AGEs) were added to cultured podocytes to imitate diabetic conditions and thus to elucidate the role of CD4 + IL-17 + T cells in renal sclerosis. Results CD80 expression was detected in early phases of DN but was absent during diffused glomerurosclerosis in DN kidney specimens. In DN samples, CD40 expression was not only observed in most of the infiltrating cells, but also increased in podocytes and tubular epithelial cells. CD40L is locally expressed on infiltrating cells. CD4 + IL-17 + T cells were found in DN, and the number of CD4 + IL-17 + T cells was positively correlated with the deterioration in glomerular filtration rate (GFR). IL-17A was the key cytokine produced by CD4 + IL-17 + T cells. IL-17A levels were elevated in DN renal tissue and were correlated with declining GFR. IL-17 and CD40L synergistically enhanced IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), transforming growth factor beta 1 (TGF-β1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) production in vitro. AGEs induced podocyte activation with increasing expression of IL-17A, CD40 and TGF-β1 in vitro. Blockade with an anti-IL-17 monoclonal antibody reduced the expression of CD40 and TGF-β1, but increased the viability of cultured podocytes. Conclusions IL-17 and CD40L synergistically mediate the inflammatory response and remodelling associated with tissue injury and glomerular sclerosis in DN.
Original language | English |
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Pages (from-to) | 248-256 |
Number of pages | 9 |
Journal | Nephrology Dialysis Transplantation |
Volume | 33 |
Issue number | 2 |
DOIs | |
State | Published - 01 02 2018 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2017 The Author . Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Keywords
- CD4 + IL-17 + T cell
- CD40L
- IL-17
- advanced glycation end-products
- diabetic nephropathy