PMID- 28339909
OWN - NLM
STAT- MEDLINE
DCOM- 20190805
LR  - 20190805
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
VI  - 33
IP  - 2
DP  - 2018 Feb 1
TI  - IL-17 and CD40 ligand synergistically stimulate the chronicity of diabetic 
      nephropathy.
PG  - 248-256
LID - 10.1093/ndt/gfw397 [doi]
AB  - 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-beta1) 
      and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) 
      production in vitro. AGEs induced podocyte activation with increasing expression 
      of IL-17A, CD40 and TGF-beta1 in vitro. Blockade with an anti-IL-17 monoclonal 
      antibody reduced the expression of CD40 and TGF-beta1, 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.
CI  - (c) The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. 
      All rights reserved.
FAU - Kuo, Huey-Liang
AU  - Kuo HL
AD  - Graduate Institute of Clinical Medical Science, College of Medicine, China 
      Medical University, Taichung, Taiwan, China.
AD  - Department of Medicine, Division of Nephrology and Kidney Institute, China 
      Medical University Hospital, Taichung, Taiwan, China.
FAU - Huang, Chiu-Ching
AU  - Huang CC
AD  - Department of Medicine, Division of Nephrology and Kidney Institute, China 
      Medical University Hospital, Taichung, Taiwan, China.
FAU - Lin, Tze-Yi
AU  - Lin TY
AD  - Department of Pathology, China Medical University Hospital, Taichung, Taiwan, 
      China.
FAU - Lin, Ching-Yuang
AU  - Lin CY
AD  - Graduate Institute of Clinical Medical Science, College of Medicine, China 
      Medical University, Taichung, Taiwan, China.
AD  - Clinical Immunological Center, Children's Hospital, China Medical University, 
      Taichung, Taiwan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Cytokines)
RN  - 0 (IL17A protein, human)
RN  - 0 (Interleukin-17)
RN  - 147205-72-9 (CD40 Ligand)
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - CD40 Ligand/*metabolism
MH  - Cells, Cultured
MH  - Chronic Disease
MH  - Cytokines/metabolism
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Diabetic Nephropathies/etiology/metabolism/*pathology
MH  - Drug Synergism
MH  - Female
MH  - Humans
MH  - Inflammation/etiology/metabolism/*pathology
MH  - Interleukin-17/*metabolism
MH  - Lymphocyte Activation
MH  - Male
MH  - Middle Aged
MH  - Podocytes/cytology/metabolism
OTO - NOTNLM
OT  - CD4+ IL-17+ T cell
OT  - CD40L
OT  - IL-17
OT  - advanced glycation end-products
OT  - diabetic nephropathy
EDAT- 2017/03/25 06:00
MHDA- 2019/08/06 06:00
CRDT- 2017/03/25 06:00
PHST- 2016/07/22 00:00 [received]
PHST- 2016/09/28 00:00 [accepted]
PHST- 2017/03/25 06:00 [pubmed]
PHST- 2019/08/06 06:00 [medline]
PHST- 2017/03/25 06:00 [entrez]
AID - 3059136 [pii]
AID - 10.1093/ndt/gfw397 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2018 Feb 1;33(2):248-256. doi: 10.1093/ndt/gfw397.