IL-17C has a pathogenic role in kidney ischemia/reperfusion injury

Wang, Feng; Yin, Jianyong; Lin, Yingying; Zhang, Fangfei; Liu, Xuanchen; Zhang, Guangyuan; Kong, Yiwei; Lu, Zeyuan; Wu, Rui; Wang, Niansong; Xing, Tao; Qian, Youcun

doi:10.1016/j.kint.2020.01.015

Cited by 25 publications

(30 citation statements)

References 49 publications

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“…IL-17 family cytokines are responsible for changes in the cytoskeleton of the podocytes, activation of inflammasome and caspases, and induction of oxidative stress and podocytes apoptosis. In addition, in tubular epithelial cells, IL-17 promotes the activation of the profibrotic pathways with the increase of the expression of TGF-β (36, 87), promotion of EMT (158) with consequent increase of extracellular matrix proteins and fibrosis (87). (C) Besides local effects, IL-17 amplifies the systemic inflammatory response by stimulating the synthesis of inflammatory cytokines, growth factors, and chemokines, resulting in granulopoiesis/myelopoiesis and recruitment of more immune cells to the kidney (31,32,194).…”

Section: The Association Between Th17/il-17 Axis Hyperactivity and Several Kidney Diseases (Other Than Lupus Nephritis)mentioning

confidence: 99%

The Th17/IL-17 Axis and Kidney Diseases, With Focus on Lupus Nephritis

Paquissi

Abensur

2021

Front. Med.

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Systemic lupus erythematosus (SLE) is a disease characterized by dysregulation and hyperreactivity of the immune response at various levels, including hyperactivation of effector cell subtypes, autoantibodies production, immune complex formation, and deposition in tissues. The consequences of hyperreactivity to the self are systemic and local inflammation and tissue damage in multiple organs. Lupus nephritis (LN) is one of the most worrying manifestations of SLE, and most patients have this involvement at some point in the course of the disease. Among the effector cells involved, the Th17, a subtype of T helper cells (CD4+), has shown significant hyperactivation and participates in kidney damage and many other organs. Th17 cells have IL-17A and IL-17F as main cytokines with receptors expressed in most renal cells, being involved in the activation of many proinflammatory and profibrotic pathways. The Th17/IL-17 axis promotes and maintains repetitive tissue damage and maladaptive repair; leading to fibrosis, loss of organ architecture and function. In the podocytes, the Th17/IL-17 axis effects include changes of the cytoskeleton with increased motility, decreased expression of health proteins, increased oxidative stress, and activation of the inflammasome and caspases resulting in podocytes apoptosis. In renal tubular epithelial cells, the Th17/IL-17 axis promotes the activation of profibrotic pathways such as increased TGF-β expression and epithelial-mesenchymal transition (EMT) with consequent increase of extracellular matrix proteins. In addition, the IL-17 promotes a proinflammatory environment by stimulating the synthesis of inflammatory cytokines by intrinsic renal cells and immune cells, and the synthesis of growth factors and chemokines, which together result in granulopoiesis/myelopoiesis, and further recruitment of immune cells to the kidney. The purpose of this work is to present the prognostic and immunopathologic role of the Th17/IL-17 axis in Kidney diseases, with a special focus on LN, including its exploration as a potential immunotherapeutic target in this complication.

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Section: The Association Between Th17/il-17 Axis Hyperactivity and Several Kidney Diseases (Other Than Lupus Nephritis)mentioning

confidence: 99%

The Th17/IL-17 Axis and Kidney Diseases, With Focus on Lupus Nephritis

Paquissi

Abensur

2021

Front. Med.

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“…It was demonstrated that NLRP3/E3 ubiquitin-protein ligase XIAP signaling aggravated renal fibrotic injury, and also NLRP3 inflammasome activation negatively regulated podocyte autophagy in diabetic nephropathy ( 10 , 11 ). Additionally, a humanized IL-6 receptor (IL-6R) antibody could reduce the activation of NLRP3 inflammasome in diabetic nephropathy, partly via suppressing IL-17A, which could be suppressed by neutralization of IL-17C in renal I/R ( 12 , 13 ). NLRP3 knockout could protect against ischemic acute kidney injury ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Tetramethylpyrazine alleviates acute kidney injury by inhibiting NLRP3/HIF‑1α and apoptosis

Sun

Wang

et al. 2020

Mol Med Rep

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The aim of the present study was to investigate the protective effect and underlying mechanism of tetramethylpyrazine (TMP) on renal ischemia reperfusion injury (RIRI) in rats, which refers to the injury caused by the restoration of blood supply and reperfusion of the kidney after a period of ischemia. Sprague-Dawley rats were randomly divided into a Sham group, renal ischemia-reperfusion (I/R) group and TMP group. TMP hydrochloride (40 mg/kg, 6 h intervals) was given via intraperitoneal injection immediately after reperfusion in the TMP group, after 24 h the kidney tissues were taken for follow-up experiments. Pathological changes in the kidney tissues were observed by periodic acid-Schiff staining. Renal function was assessed by measuring levels of serum creatinine and blood urea nitrogen, and inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6. Renal cell apoptosis was detected by TUNEL-DAPI double staining, mRNA and protein changes were analyzed by reverse transcription-quantitative PCR and western blotting. Cell viability was measured using a CCK-8 assay. It was found that the renal tissues of the sham operation group were notably abnormal, and the renal tissues of the I/R group were damaged, while the renal tissues of the TMP group were less damaged compared with those of the I/R group. Compared with the I/R group, the serum creatinine and blood urea nitrogen levels in the TMP group were low (all P<0.05), levels of inflammatory cytokines TNF-α and IL-6 decreased, the apoptotic rate was low (all P<0.05), and the relative expression levels of nucleotide-oligomerization domain-like receptor 3 (NLRP3) protein and mRNA in renal tissues were low (all P<0.05). The expression levels of hypoxia-inducible factor 1-α and NLRP3 increased after oxygen and glucose deprivation (OGD), and reduced after treatment with OGD and TMP (all P<0.05). It was concluded that TMP can reduce renal injury and improve renal function in RIRI rats, and its mechanism may be related to the reduction of NLRP3 expression in renal tissues.

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“…The influx of Th17 cells in the setting of AKI may be due in part to the activation of CCL20 [88]. In addition, a recent study suggests that damaged renal tubules produce IL-17C, which may recruit Th17 cells to promote inflammation via binding to the receptor IL-17RE [89]. The precise mechanisms by which Th17 cells contribute to renal injury are not clear, but are likely related to an overall inflammatory response leading to recruitment of effectors cells or contributions to vascular congestion and hypoxia.…”

Section: Responses In Acute Injurymentioning

confidence: 99%

T helper 17 cells in the pathophysiology of acute and chronic kidney disease

Basile

Ullah

Collet

et al. 2021

Kidney Res Clin Pract

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As of 2017, the global burden of chronic kidney disease (CKD) was estimated to be approximately 9.1%, indicating that CKD is a significant healthcare concern worldwide. Global age-adjusted mortality rates for patients with CKD have declined in the last 30 years, and quality of life metrics decrease as glomerular filtration rate declines [1]. In the period between1990 and 2017, there was an approximate 41% increase in the number of patients with end-stage renal disease (ESRD). Despite this, CKD patients are more likely to die due to complications such as hypertension, cardiovascular disease, anemia, and bone and mineral Both acute and chronic kidney disease have a strong underlying inflammatory component. This review focuses primarily on T helper 17 (Th17) cells as mediators of inflammation and their potential to modulate acute and chronic kidney disease. We provide updated information on factors and signaling pathways that promote Th17 cell differentiation with specific reference to kidney disease. We highlight numerous clinical studies that have investigated Th17 cells in the setting of human kidney disease and provide updated summaries from various experimental animal models of kidney disease indicating an important role for Th17 cells in renal fibrosis and hypertension. We focus on the pleiotropic effects of Th17 cells in different renal cell types as potentially relevant to the pathogenesis of kidney disease. Finally, we highlight studies that present contrasting roles for Th17 cells in kidney disease progression.

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IL-17C has a pathogenic role in kidney ischemia/reperfusion injury

Cited by 25 publications

References 49 publications

The Th17/IL-17 Axis and Kidney Diseases, With Focus on Lupus Nephritis

The Th17/IL-17 Axis and Kidney Diseases, With Focus on Lupus Nephritis

Tetramethylpyrazine alleviates acute kidney injury by inhibiting NLRP3/HIF‑1α and apoptosis

T helper 17 cells in the pathophysiology of acute and chronic kidney disease

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