Imbalance of regulatory T cells to Th17 cells in IgA nephropathy

Lin, Fujun; Jiang, Gengru; Shan, Jian-Ping; Zhu, Chun Fang; Zou, Jun; Wu, Xiangru

doi:10.3109/00365513.2011.652158

Cited by 72 publications

(65 citation statements)

References 29 publications

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“…42 Our flow cytometry studies suggest that increased IL-17 + neutrophils could be a potential source for increased IL-17 in THP 2/2 kidneys. At this time, we cannot completely rule out additional sources of increased IL-17 in THP 2/2 kidneys such as parenchymal or stromal cells, 43 and this is currently the topic ongoing investigations in the laboratory.…”

Section: Discussionmentioning

confidence: 98%

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

Micanovic¹,

Chitteti

Dagher³

et al. 2015

Journal of the American Society of Nephrology

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Tamm-Horsfall protein (THP) is a glycoprotein uniquely expressed in the kidney. We recently showed an important role for THP in mediating tubular cross-talk in the outer medulla and in suppressing neutrophil infiltration after kidney injury. However, it remains unclear whether THP has a broader role in neutrophil homeostasis. In this study, we show that THP deficiency in mice increases the number of neutrophils, not only in the kidney but also in the circulation and in the liver, through enhanced granulopoiesis in the bone marrow. Using multiplex ELISA, we identified IL-17 as a key granulopoietic cytokine specifically upregulated in the kidneys but not in the liver of THP 2/2 mice. Indeed, neutralization of IL-17 in THP 2/2 mice completely reversed the systemic neutrophilia. Furthermore, IL-23 was also elevated in THP 2/2 kidneys. We performed real-time PCR on laser microdissected tubular segments and FACS-sorted renal immune cells and identified the S3 proximal segments, but not renal macrophages, as a major source of increased IL-23 synthesis. In conclusion, we show that THP deficiency stimulates proximal epithelial activation of the IL-23/IL-17 axis and systemic neutrophilia. Our findings provide evidence that the kidney epithelium in the outer medulla can regulate granulopoiesis. When this novel function is added to its known role in erythropoiesis, the kidney emerges as an important regulator of the hematopoietic system.

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Section: Discussionmentioning

confidence: 98%

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

Micanovic¹,

Chitteti

Dagher³

et al. 2015

Journal of the American Society of Nephrology

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“…It was shown that patients with MsPGN have increased peripheral Th17 cells and serum or urinary IL-17 levels [23, 24], CD4 T cells and Th1 cytokines also contribute to the development of the Thy-1 nephritis model, and the suppression of cytokine production could be a valid target for therapy [25-27]. The cell cycle protein kinase inhibitor p27 kip1 negatively regulates the cell cycle [28].…”

Section: Discussionmentioning

confidence: 99%

Effect of Huaier On the Proliferation of Mesangial Cells in Anti-Thy-1 Nephritis

Bai¹,

Wang²,

Mei³

et al. 2017

Cell Physiol Biochem

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Background/Aims: To determine whether an aqueous extract of Trametes robiniophila Murr. (Huaier) suppresses anti-Thy-1 mesangial proliferative glomerulonephritis (MsPGN) in vivo and platelet-derived growth factor (PDGF)-BB–induced mesangial cell proliferation in vitro. Methods: Male Wistar rats were randomly categorized into 5 groups: Sham, Thy-1, and 3 Huaier-treated groups (low, medium, and high dose). Two weeks after treatment, urinary proteins were quantified and renal pathological changes were examined. MAX interactor 1 (Mxi-1) and proliferating cell nuclear antigen (PCNA) expression levels in isolated glomeruli, rat mesangial cell viability, cell-cycle distribution, and cell-cycle pathways were assessed. Results: Huaier diminished the proliferative damages and urinary protein secretion in Thy-1 rats. PCNA was downregulated, whereas Mxi-1 was upregulated in the isolated glomeruli of Huaier-treated groups compared with the Thy-1 group. Huaier inhibited PDGF-BB– stimulated proliferation of rat mesangial cells in a time- and dose-dependent manner (50% inhibitory concentration = 6.19 mg/mL) and induced G2 cell-cycle arrest. Cell-cycle pathway proteins were downregulated, whereas Mxi-1 was upregulated in Huaier-treated mesangial cells compared with PDGF-BB–stimulated cells. Conclusion: Huaier reduces urinary protein excretion and relieves hyperplasia in mesangial cells in anti-Thy-1 MsPGN as well as inhibits PDGF-BB–stimulated proliferation and DNA synthesis of rat mesangial cells in vitro, suggesting its novel therapeutic potential in MsPGN.

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“…These are IL-17-producing Th17 cells that contribute to the progression of inflammation [10, 11] and Foxp3 + T regulatory cells which are natural suppressors that control overactive cells [12, 13]. A balance between Th17 and Treg subsets is crucial for immune homeostasis, however it was shown to be impaired in various clinical disorders [14–20]. The balance between Tregs and Th17 is controlled by IL-6.…”

Section: Introductionmentioning

confidence: 99%

The Serum IL-6 Profile and Treg/Th17 Peripheral Cell Populations in Patients with Type 1 Diabetes

Ryba-Stanisławowska

Skrzypkowska

Myśliwska

et al. 2013

Mediators of Inflammation

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IL-6 is a pleiotropic cytokine involved in the regulation of the immune response, inflammation, and hematopoeisis. Its elevated levels are found in a range of autoimmune and chronic inflammatory diseases. IL-6 is also involved in regulation of the balance between two T cell subsets: Tregs and Th17, which have contradictory functions in the control of inflammation. The present study provides a quantitative analysis regarding the Th17/Treg cell balance in peripheral blood of children with type 1 diabetes and its association with serum IL-6 level.

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Imbalance of regulatory T cells to Th17 cells in IgA nephropathy

Abstract: Imbalance of Treg/Th17 found in IgAN may play a role in disease pathogenesis and progression.

Cited by 72 publications

References 29 publications

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

Effect of Huaier On the Proliferation of Mesangial Cells in Anti-Thy-1 Nephritis

The Serum IL-6 Profile and Treg/Th17 Peripheral Cell Populations in Patients with Type 1 Diabetes

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