Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7–CTLA-4 and CCL-CCR pathways

Gan, Lu; Zhou, Qiaoling; Li, Xiaozhao; Chen, Chen; Meng, Ting; Pu, Jiaxi; Zhu, Mengyuan; Xiao, Chenggen

doi:10.1007/s11010-017-3185-8

Cited by 22 publications

(15 citation statements)

References 25 publications

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“…Moreover, elevation of Th22 cells in patients’ peripheral blood was associated with worse histologic renal images; the percentage of Th22 cells was positively correlated with MEST scores. Authors concluded that tonsillitis aggravated renal injury in IgAN through induction of Th22 lymphocytosis, infiltration of renal tissue, and promotion of renal fibrosis by Th22 [16, 76].…”

Section: Renal Injury—th2 Th17 Th22 and Treg Cells Participation Inmentioning

confidence: 99%

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

et al. 2018

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Background Immunoglobulin A nephropathy (IgAN), the most frequent cause of primary glomerulonephritis worldwide, is an autoimmune disease with complex pathogenesis. In this review, we focus on T cells and summarize knowledge about their involvement in pathophysiology and treatment of IgAN Methods We reviewed the literature for (1) alterations of T cell subpopulations in IgAN, (2) experimental and clinical proofs for T cells’ participation in IgAN pathogenesis, (3) clinical correlations with T cell-associated alterations, and (4) influence of drugs used in IgAN therapy on T cell subpopulations. Results We found that IgAN is characterized by higher proportions of circulatory Th2, Tfh, Th17, Th22 and γδ T cells, but lower Th1 and Treg cells. We discuss genetic and epigenetic makeup that may contribute to this immunological phenotype. We found that Th2, Th17 and Tfh-type interleukins contribute to elevated synthesis of galactose-deficient IgA1 (Gd-IgA1) and that the production of anti-Gd-IgA1 autoantibodies may be stimulated by Tfh cells. We described the roles of Th2, Th17, Th22 and Treg cells in the renal injury and summarized correlations between T cell-associated alterations and clinical features of IgAN (proteinuria, reduced GFR, hematuria). We detailed the impact of immunosuppressive drugs on T cell subpopulations and found that the majority of drugs have nonoptimal influence on T cells in IgAN patients. Conclusions T cells play an important role in IgAN pathogenesis and are correlated with its clinical severity. Clinical trials with the drugs targeting the reported alterations of the T-cell compartment are highly desirable.

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Section: Renal Injury—th2 Th17 Th22 and Treg Cells Participation Inmentioning

confidence: 99%

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

et al. 2018

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“…4,5 However, IgAN was considered as one complex multifactorial disease, immunology and genetics mechanisms were proved to play critical roles in the development and pathogenesis of IgAN. [6][7][8] Growing evidences suggested that B lymphocytes were increased in cases with high concentration of the IgA in the serum. 6,9 IgA1 in the serum is abnormally O-glycosylated, which causes IgA1 mesangial deposition and glomerular injury developing into IgAN.…”

Section: Introductionmentioning

confidence: 99%

MiR‐320 promotes B cell proliferation and the production of aberrant glycosylated IgA1 in IgA nephropathy

Shi

Zhao

2018

J of Cellular Biochemistry

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IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. However, the etiology of this disease is complex and the pathogenesis of IgAN is still unknown. MicroRNAs (miRNAs) play important roles in a lot of pathological and physiological processes. In this study, we showed that the expression of miR-320 was significantly upregulated in renal tissues and urinary of IgAN patients. Moreover, the intra-renal expression level of miR-320 had significant correlation with miR-320 expression in the urinary of IgAN patients. Overexpression of miR-320 increased B cell proliferation and promoted cyclin D1 expression. Furthermore, we identified that PTEN was direct target gene of miR-320 in the B cell. Ectopic expression of miR-320 suppressed PTEN expression. Overexpression of miR-320 decreased Cosmc expression in the B cell. In addition, we demonstrated that Cosmc expression was significantly downregulated in the renal tissues and urinary of IgAN patients. The intra-renal expression level of Cosmc had significant correlation with Cosmc expression of urinary in IgAN patients. We proved that the expression level of Cosmc was negatively correlated with the expression of miR-320 in the renal tissues of IgAN patients. Overexpression of miR-320 promoted the B cell proliferation through suppressing PTEN expression. Taken together, these data suggested that miR-320 acted an important role in the development of IgAN.

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“…IL-22 is mainly secreted by lymphoid cells such as Th22, Th17, NKT and innate lymphoid cells (ILCs) [32], Th22. Recent studies have reported the reno-protective effects of IL-22 in acute kidney injury and CKD [20,21], however we and other groups verified that Th22 and IL-22 promoted renal damage in IgA nephropathy and hypertension [33][34][35][36]. Whether IL-22 is protective or destructive in kidney diseases may depend on different microenvironment.…”

Section: Discussionmentioning

confidence: 68%

Interleukin-22 attenuates renal tubular cells inflammation and fibrosis induced by TGF-β1 through Notch1 signaling pathway

Tang

Xiao

et al. 2020

Renal Failure

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2020) Interleukin-22 attenuates renal tubular cells inflammation and fibrosis induced by TGF-β1 through Notch1 signaling pathway, Renal Failure, 42:1, 381-390, ABSTRACTTransforming growth factor-b1 (TGF-b1) is a crucial factor implicated in the development of renal inflammation and tubulointerstitial fibrosis (TIF). The cytokine interleukin 22 (IL-22) was previously reported to involve in the pathogenesis of chronic inflammatory diseases, however recent studies showed that IL-22 could reduced inflammatory responses and tissue damage. In the present study, we aim to investigate the role and mechanisms of IL-22 in renal tubular cells inflammation and fibrosis induced by TGF-b1. HK-2 cells were treated with TGF-b1 in the presence of IL-22 or the Notch pathway inhibitor dibenzazepine (DBZ) for 48 h. Collagen I (Col I), fibronectin (FN), a-smooth muscle actin (a-SMA), vimentin and E-Cadherin were detected by western blot, proinflammatory factors (TNF-a, IL-6) and chemokines (MCP-1, RANTES) were evaluated by ELISA. Jagged1, Notch1, NICD1, and Hes1 were also detected by western blot. We found TGF-b1 increased the levels of Col I, FN, a-SMA and vimentin in HK-2 cells compared with control, and decreased E-Cadherin level, however, IL-22 restored their expressions partly. IL-22 reduced overexpression of proinflammatory factors (TNF-a, IL-6) and chemokines (MCP-1, RANTES) levels induced by TGF-b1, along with down-regulation of Jagged1, Notch, NICD1 and Hes1. Fibrosis and inflammation in renal tubular cells induced by TGF-b1 could be attenuated by IL-22, and the effects were similar to DBZ treatment. Collectively, our study shows that IL-22 exerts a protective role in renal fibrotic and inflammatory responses induced by TGF-b1 in vitro, which may be through inhibiting Jagged1/Notch1 signaling pathway activation. ARTICLE HISTORY

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Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7–CTLA-4 and CCL-CCR pathways

Cited by 22 publications

References 25 publications

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

MiR‐320 promotes B cell proliferation and the production of aberrant glycosylated IgA1 in IgA nephropathy

Interleukin-22 attenuates renal tubular cells inflammation and fibrosis induced by TGF-β1 through Notch1 signaling pathway

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