Losartan and Dexamethasone may inhibit chemotaxis to reduce the infiltration of Th22 cells in IgA nephropathy

Xiao, Chenggen; Zhou, Qiaoling; Li, Xiaozhao; Li, Hui; Zhong, Yong; Meng, Ting; Zhu, Mengyuan; Sun, Hong; Liu, Shuang; Tang, Rong; Pu, Jiaxi; Xu, Yan; Xiao, Ping

doi:10.1016/j.intimp.2016.11.025

Cited by 19 publications

(20 citation statements)

References 34 publications

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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: 69%

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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Section: Discussionmentioning

confidence: 69%

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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“…It was found that both drugs differentially reduced the number of Th22 cells after 1 month, and mesangial cell proliferation was also improved. Meanwhile, the expression of IL-22, CCR10 and CCL27 was decreased following treatment with either drug (85). In summary, based on the aforementioned research, similar to Th17 cells, Th22 cells and secreted serum IL-22 levels may be exacerbating factors in patients with IgAN.…”

Section: Th22 Cellsmentioning

confidence: 79%

“…Furthermore, TWG showed therapeutic effects in IgAN rats and may regulate the immune balance of Th17 and Tregs as they significantly decreased the serum levels of IL-17 and increased the number of Tregs in the blood. Xiao et al (85) reported that, in a mouse model of IgAN, losartan and dexamethasone differentially decreased the number of Th22 cells after 1 month, and mesangial cell proliferation was also improved. Meanwhile, Zhang et al (23) reported that treatment with prednisone significantly reduced the number of CD4 + CXCR5 + and CD4 + CXCR5 + PD-1 + TFH cells and the serum level of IL-21, but the treatment increased IL-4 and IL-10 in patients with IgAN.…”

Section: Imbalance Of T Cell Subsets As a Target For The Treatment Ofmentioning

confidence: 99%

T lymphocytes in IgA nephropathy (Review)

Tang

et al. 2020

Exp Ther Med

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Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis worldwide, is the main cause of end-stage renal disease. IgAN is characterized by the accumulation of immune complexes in the circulation, which contain abnormal levels of IgA. IgAN primarily results from galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1 deposition in the renal mesangium, causing local proliferation and matrix expansion. Gd-IgA1 has been confirmed as one of the key effectors in the pathogenesis of IgAN, but the origin of Gd-IgA1 is not clear. Recent studies have shown that Gd-IgA1 deposition could be the result of mucosally primed plasma cells and is associated with T cell dysregulation. T cells contribute to the IgA response and play an important role in the development of IgAN. In the present review, the latest discoveries regarding the role of T lymphocytes in the pathogenesis of IgAN have been summarized. Understanding these advances will allow novel therapeutic strategies for the treatment of IgAN.

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“…Similarly, Lu et al found that renal mesangial cells and renal tubular epithelial cells induced the infiltration of Th22 cells (45). Renal mesangial cells have an important function in the glomerulus, and they can interact with immune deposits, complement components, and inflammatory mediators (46). The proliferation of mesangial cells and the excessive production of mesangial matrix are typical manifestations of renal biopsies in patients with active LN (47).…”

Section: Discussionmentioning

confidence: 94%

Th22 Cells Promote in vitro Proliferation and Cytokine Secretion in HaCaT and HRMC cells via Production of IL-22 and Stimulation of PI3K/AKT Signaling

Zhao¹,

Sun²,

Liu³

et al. 2020

Preprint

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Background: T helper (Th) 22 cells function in the pathogenesis of systemic lupus erythematosus (SLE), but their exact role remains unclear. We examined in vitro interactions of Th22 cells with different target cells.Methods: Flow cytometry was used to isolate Th22 cells from the peripheral blood mononuclear cells (PBMCs) of 5 healthy subjects. The optimal co-culture ratio of effector:target (E:T) cells and the optimal co-culture concentration of recombinant interleukin (rIL) -22 were determined. The levels of IL-22, proliferation of target cells, and the levels proinflammatory cytokines in different culture systems with human keratinocyte cells (HaCaT) and human renal mesangial cells (HRMC) were determined. Western blotting was used to assess changes in the levels of proteins in the PI3K/AKT pathway.Results: The levels of IL-22 were greater when HaCaT and HRMC cells were co-cultured with Th22 cells or rIL-22, and co-culturing with contact had a greater effect than co-culturing without contact. The levels of cytokines were also significantly greater when target cells were co-cultured with Th22 cells. IL-22mAb reversed the effect of IL-22. Th22 cells significantly activated PI3K/AKT signaling in HaCaT and HRMC cells; LY294002 (an inhibitor of this pathway) reversed this effect and also downregulated the levels of proinflammatory cytokines; IL-22mAb had a similar but weaker effect. Conclusions: Our results suggest that Th22 cells promote cell proliferation and secretion of pro-inflammatory cytokines of their target cells via IL-22-mediated stimulation of PI3K/AKT signaling.

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Losartan and Dexamethasone may inhibit chemotaxis to reduce the infiltration of Th22 cells in IgA nephropathy

Cited by 19 publications

References 34 publications

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

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

T lymphocytes in IgA nephropathy (Review)

Th22 Cells Promote in vitro Proliferation and Cytokine Secretion in HaCaT and HRMC cells via Production of IL-22 and Stimulation of PI3K/AKT Signaling

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