DC-SIGN reacts with TLR-4 and regulates inflammatory cytokine expression via NF-κB activation in renal tubular epithelial cells during acute renal injury

Feng, D; Wang, Y; Liu, Y; Wu, Ling; Li, X; Chen, Y; Che, Xu; Yang, Ke; Zhou, Tong

doi:10.1111/cei.13048

Cited by 24 publications

(17 citation statements)

References 33 publications

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“…Damage-associated molecular patterns can be transferred into renal tubular epithelial cells trough EVs (138) and prevent tubular recovery (139,140). Pathogen-associated molecular patterns, such as LPS, upregulate the expression of DC-SIGN and toll-like receptor 4, stimulating tubular secretion of IL-6 and TNFα (141).…”

Section: Renal Tubular Epithelial Cellsmentioning

confidence: 99%

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

et al. 2020

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Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens, costimulatory/inhibitory molecules, cytokines, growth factors, and functional microRNAs (miRNAs) that may modulate expression of recipient cell genes. As paracrine factors, neutrophil-and macrophage-derived EVs exert immunosuppressive and immune-stimulating effects on dendritic cells, respectively. Dendritic cell-derived EVs mediate alloantigen spreading and modulate antigen presentation to T lymphocytes. At systemic level, EVs exert pleiotropic effects on complement and coagulation. Depending on their biogenesis, they can amplify complement activation or shed complement inhibitors and prevent cell lysis. Likewise, endothelial-and platelet-derived EVs can exert procoagulant/prothrombotic effects and also promote endothelial survival and angiogenesis after ischemic injury. Kidney endothelial-and tubular-derived EVs play a key role in ischemia-reperfusion injury (IRI) and during the healing process; additionally, they can trigger rejection by inducing both alloimmune and autoimmune responses. Endothelial EVs have procoagulant/pro-inflammatory effects and can release sequestered self-antigens, generating a tissue-specific autoimmunity. Renal tubule-derived EVs shuttle pro-fibrotic mediators (TGF-β and miR-21) to interstitial fibroblasts and modulate neutrophil and T-lymphocyte influx. These processes can lead to peritubular capillary rarefaction and interstitial fibrosis-tubular atrophy. Different EVs, including those from mesenchymal stromal cells (MSCs), have been employed as a therapeutic tool in experimental models of rejection and IRI. These particles protect tubular and endothelial cells (by inhibition of apoptosis and inflammation-fibrogenesis or by inducing autophagy) and stimulate tissue regeneration (by triggering angiogenesis, cell proliferation, and migration). Finally, urinary and serum EVs represent potential biomarkers for delayed graft function (DGF) and acute rejection. In conclusion, EVs sustain an intricate crosstalk between graft tissue and innate/adaptive immune systems. EVs play a major role in allorecognition, IRI, autoimmunity, and alloimmunity and are promising as biomarkers and therapeutic tools in KT.

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Section: Renal Tubular Epithelial Cellsmentioning

confidence: 99%

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

et al. 2020

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“…Moreover, many pathogens are capable of diverting the system to inhibit or modulate the immune response using these pathways [61]. Engagement of DC-SIGN by pathogens with mannose structures, like Candida albicans, human immunodeficiency virus-1, and M. tuberculosis, modulates TLR4 [62] and TLR2 signaling pathways in particular. M. tuberculosis and M. bovis are also able to produce mannose-capped lipoarabinomannan (ManLAM), a glycolipid targeting DC-SIGN that interferes with TLR2 signaling, thereby inducing IL-10 secretion by DCs [62,63].…”

Section: Pathogen-induced Immune Tolerancementioning

confidence: 99%

“…Engagement of DC-SIGN by pathogens with mannose structures, like Candida albicans, human immunodeficiency virus-1, and M. tuberculosis, modulates TLR4 [62] and TLR2 signaling pathways in particular. M. tuberculosis and M. bovis are also able to produce mannose-capped lipoarabinomannan (ManLAM), a glycolipid targeting DC-SIGN that interferes with TLR2 signaling, thereby inducing IL-10 secretion by DCs [62,63]. In this context, DC-SIGN activation by ManLAM also modulates the TLR4-mediated NFκB signaling pathway and modifies the IL-10/IL-12p70 secretion balance in favor of IL-10 to promote the infection.…”

Section: Pathogen-induced Immune Tolerancementioning

confidence: 99%

Tethering Innate Surface Receptors on Dendritic Cells: A New Avenue for Immune Tolerance Induction?

Lamendour

Deluce-Kakwata-Nkor

Mouline

et al. 2020

IJMS

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Dendritic cells (DCs) play a key role in immunity and are highly potent at presenting antigens and orienting the immune response. Depending on the environmental signals, DCs could turn the immune response toward immunity or immune tolerance. Several subsets of DCs have been described, with each expressing various surface receptors and all participating in DC-associated immune functions according to their specific skills. DC subsets could also contribute to the vicious circle of inflammation in immune diseases and establishment of immune tolerance in cancer. They appear to be appropriate targets in the control of inflammatory diseases or regulation of autoimmune responses. For all these reasons, in situ DC targeting with therapeutic antibodies seems to be a suitable way of modulating the entire immune system. At present, the field of antibody-based therapies has mainly been developed in oncology, but it is undergoing remarkable expansion thanks to a wide variety of antibody formats and their related functions. Moreover, current knowledge of DC biology may open new avenues for targeting and modulating the different DC subsets. Based on an update of pathogen recognition receptor expression profiles in human DC subsets, this review evaluates the possibility of inducing tolerant DCs using antibody-based therapeutic agents.

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“…Among these factors, the early inflammation responses in kidneys are increasingly recognized as a major mechanism of sepsis-induced AKI. Previous studies have indicated that endotoxins, such as lipopolysaccharide (LPS), bind to Toll-like receptor 4 (TLR4), leading to the activation of the NF- κ B pathway in septic AKI, and these processes are initiated a few hours with the production of cytokines, such as TNF-a and IL-1, and the infiltration and activation of immune cells [ 8 , 9 ]. Castoldi et al reported that TLR2, TLR4, and MyD88 mRNAs are highly expressed in the renal tissue after sepsis.…”

Section: Introductionmentioning

confidence: 99%

Negative Regulation of Tec Kinase Alleviates LPS-Induced Acute Kidney Injury in Mice via theTLR4/NF-κB Signaling Pathway

Zhang

Zhou

Jiang

et al. 2020

BioMed Research International

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Tec kinase is an important mediator in inflammatory immune response that enhances the activity of neutrophils and macrophages. However, information on its function in lipopolysaccharide- (LPS-) induced acute kidney injury (AKI) is limited. This study is aimed at determining whether Tec kinase was a regulator in AKI. An AKI model in mice was successfully established using intraperitoneal LPS. Results showed that the serum levels of creatinine (Cr), blood urea nitrogen (BUN), and cystatin-C (Cys-C) increased after intraperitoneal LPS injection. Renal tissue sustained significantly severe injury as measured by pathological scores. Pretreatment with LFM-A13 improved the function of the kidney in mice and decreased the renal injury score. Enzyme-linked immunosorbent assay showed that LFM-A13 significantly reduced the release of IL-1β and TNF-α in mice exposed to LPS. LFM-A13 can evidently abrogate the expression of Tec protein, MyD88, TLR4, NF-κB p65, and Tec’s phosphorylated protein as determined by Western blot. Immunohistochemistry analysis revealed that LFM-A13 markedly downregulated the expression of Tec kinase in renal tubular epithelial cells. In vitro, Tec kinase protein was expressed highly in NRK-52E cells after LPS exposure. Tec-siRNA also decreased IL-1β and TNF-α production and obviously abolished phospho-p65 and phospho-IκBα expression in NRK-52E cell stimulated by LPS; however, Tec-siRNA increased the IκBα level. Altogether, these data suggested that Tec kinase can be a modulating protein in AKI through TLR4/NF-κB activation.

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DC-SIGN reacts with TLR-4 and regulates inflammatory cytokine expression via NF-κB activation in renal tubular epithelial cells during acute renal injury

Cited by 24 publications

References 33 publications

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

Tethering Innate Surface Receptors on Dendritic Cells: A New Avenue for Immune Tolerance Induction?

Negative Regulation of Tec Kinase Alleviates LPS-Induced Acute Kidney Injury in Mice via theTLR4/NF-κB Signaling Pathway

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