Delayed ischaemic preconditioning in the presence of galectin‐9 protects against renal ischaemic injury through a regulatory T‐cell dependent mechanism

Zhang, Bing-Ying; Fang, Yi; Jiao, Xiaoyan; Wu, Songquan; Cai, Jing; Zou, Jianzhou; Ding, Xiaoqiang

doi:10.1111/nep.12680

Cited by 7 publications

(5 citation statements)

References 24 publications

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“…Previously we have proved that the renoprotective effect of delayed IPC was partially through a mechanism related to the expansion of Treg cells [8]. Here we found that CD28sa mimicked the renoprotective effects of IPC on kidneys, and in some respects, even better.…”

Section: Resultssupporting

confidence: 58%

“…For the latter, one of the protective mechanisms of IPC involves the upregulation of Treg cells, which negatively regulate the excessive inflammatory reaction in renal ischemic injury [11]. Our previous studies have clarified that IPC also breaks the balance of AKI to some extent [8,12]. Unlike the other immunomodulatory agents, the superagonistic CD28-specific monoclonal antibody (CD28sa MAb, clone: D665) can activate T cells and expand Treg cells selectively without recognition of the first signal by the T-cell receptor [13].…”

mentioning

confidence: 99%

“…The molecular mechanisms of regulating the Treg cell numbers are multiple and complex, and there were various strategies reported to augment Treg numbers including the administration of N,N-dimethylsphingosine [6], FTY720 [7], galectin-9 [8], parenchymal stem cells [9], heat shock protein pretreatment [10,] and ischemic preconditioning (IPC) [11]. For the latter, one of the protective mechanisms of IPC involves the upregulation of Treg cells, which negatively regulate the excessive inflammatory reaction in renal ischemic injury [11].…”

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confidence: 99%

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Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell

Liang

Kuang

et al. 2017

Am J Nephrol

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Background: Regulatory T (Treg) cells are a highly suppressive subset of CD4⁺ lymphocytes and have recently been proved to be crucial to suppress the inflammatory responses of ischemic kidney injury. CD28 superagonists (CD28sa) are monoclonal antibodies that preferentially expand Treg cells without a T-cell receptor and a costimulatory signal. This study aims to test the protection and discover the mechanisms of CD28sa treatment against renal ischemia-reperfusion (IR) injury (IRI). Methods: Male C57BL/6N mice were treated with CD28sa via peritoneal injection (0.1 mg) 6 days before the induction of IRI, or with 18-min ischemic precondition (IPC). IRI was induced by bilateral clamping of renal pedicles for 35 min followed by reperfusion. The role of Treg expansion in renal protection conferred by CD28sa treatment was examined using anti-CD25 antibody. Results: CD28sa treatment alone significantly increased the percentage of Treg cells in the spleen (18.10 ± 2.00 vs. 6.64 ± 0.86%, p < 0.01), peripheral blood (16.43 ± 5.94 vs. 2.57 ± 1.09%, p < 0.01), and kidney (2.69 ± 0.90 vs. 0.53 ± 0.14%, p < 0.01) of C57BL/6N mice 6 days after the administration. Mice pretreated with CD28sa or IPC had less renal injury at 24 h after IRI with attenuation of renal tubular damage and lower serum creatinine compared with the mice that underwent renal IRI alone. The number of infiltrating macrophages in the kidney and IFN-γ secreting CD4⁺ T cells in peripheral blood were diminished in the CD28sa-IR group and the IPC-IR group. The renal protection bestowed by CD28sa or IPC was abolished by anti-CD25 antibody administration. Conclusions: Treg expansion induced by CD28sa ameliorated renal IRI.

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Section: Resultssupporting

confidence: 58%

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confidence: 99%

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confidence: 99%

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Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell

Liang

Kuang

et al. 2017

Am J Nephrol

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“…Tim-3 may affect acute kidney injury by regulating Treg cells and further participate in the progression of chronic kidney disease [51]. In renal IRI, Zhan et al [54] found that the protective effect of delayed ischemic preconditioning combined with Gal-9 is better than that of ischemic preconditioning alone, and its effect is mediated by the expansion of Treg cells. Mesenchymal stem cells attenuate sepsis-associated acute kidney injury by the induction of Tregs and inhibition of Th17 cells via the Gal-9/Tim-3 pathway [55].…”

Section: Discussionmentioning

confidence: 99%

Gal-9/Tim-3 signaling pathway activation suppresses the generation of Th17 cells and promotes the induction of Foxp3+regulatory T cells in renal ischemia-reperfusion injury

Tao

WANG

Feng

et al. 2022

Preprint

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CD4+T cells mediate the pathogenesis of renal ischemia-reperfusion injury (IRI). Emerging research suggests that a Th17/regulatory T cell (Treg) imbalance plays a pivotal role in the development of renal IRI. The recently identified negative checkpoint T cell immunoglobulin domain and mucin domain family 3 (Tim-3) inhibits the immune response by binding to its ligand, galectin-9 (Gal-9). However, the role of the Gal-9/Tim-3 signaling pathway in the regulation of CD4+T cell subsets in renal IRI remains unclear. In this study, the effect of the Gal-9/Tim-3 signaling pathway on Th17/Treg subsets in renal IRI was investigated using a mouse model. Renal IRI induced the expression of Gal-9 in renal tubular epithelial cells and increased the percentages of Tim-3+Th17 cells and Tim-3+Foxp3+Treg cells in the IR kidneys. The administration of rAAV9-Gal-9 suppressed kidney inflammation, reduced the mortality of mice with renal IRI, increased Foxp3+Treg cells, and reduced Th17 cells. In contrast, the blockade of Tim-3 in vivo with an anti-Tim-3 mAb aggravated renal inflammation, decreased Foxp3+Treg cells, and promoted Th17 cells. Thus, Gal-9/Tim-3 signaling pathway activation may protect against renal IRI by inhibiting Th17 cell production and inducing Foxp3+Treg cell expansion. Our study suggests that the Gal-9/Tim-3 signaling pathway might become a target of immunotherapy in renal IRI.

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“…Galectin-9 is a ␤-galactoside binding protein, which is a urate transporter in the kidneys, is also expressed in myeloid cells, and is known for its role in dendritic cell maturation and inducing apoptosis of promoting iTreg differentiation (151). Combination of galectin-9 pretreatment with ischemic preconditioning offered better protection from IRI than ischemic preconditioning alone (271). The protection correlated with a decrease in IFN␥-producing CD4 ϩ T cells and an increase in the proportion of Foxp3 ϩ Tregs in peripheral blood, spleen, and kidneys.…”

Section: F685mentioning

confidence: 99%

Regulatory T cells in acute and chronic kidney diseases

Sharma

Kinsey

2018

American Journal of Physiology-Renal Physiology

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Foxp3-expressing CD4 regulatory T cells (Tregs) make up one subset of the helper T cells (Th) and are one of the major mechanisms of peripheral tolerance. Tregs prevent abnormal activation of the immune system throughout the lifespan, thus protecting from autoimmune and inflammatory diseases. Recent studies have elucidated the role of Tregs beyond autoimmunity. Tregs play important functions in controlling not only innate and adaptive immune cell activation, but also regulate nonimmune cell function during insults and injury. Inflammation contributes to a multitude of acute and chronic diseases affecting the kidneys. This review examines the role of Tregs in pathogenesis of renal inflammatory diseases and explores the approaches for enhancing Tregs for prevention and therapy of renal inflammation.

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Delayed ischaemic preconditioning in the presence of galectin‐9 protects against renal ischaemic injury through a regulatory T‐cell dependent mechanism

Abstract: The renoprotective effect of delayed IPC combined with galectin-9 was superior to IPC alone, through a mechanism related to expansion of regulatory T cells.

Cited by 7 publications

References 24 publications

Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell

Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell

Gal-9/Tim-3 signaling pathway activation suppresses the generation of Th17 cells and promotes the induction of Foxp3+regulatory T cells in renal ischemia-reperfusion injury

Regulatory T cells in acute and chronic kidney diseases

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