Competitive binding of CD226/TIGIT with poliovirus receptor regulates macrophage polarization and is involved in vascularized skin graft rejection

Zhang, Dongliang; Liu, Yitian; Ma, Jingchang; Xu, Zheng; Duan, Chujun; Wang, Yuling; Li, Xuemei; Han, Juntao; Zhuang, Ran

doi:10.1016/j.ajt.2023.04.007

Cited by 4 publications

(4 citation statements)

References 48 publications

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“…6 A). Studies have reported that activation of MSK1 can promote M2 macrophage polarization [ 35 ]. Furthermore, studies have revealed that the knocking out MSK1 enhances macrophage responsiveness to LPS and increases their inflammatory response [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

Exosomal miR-155-5p drives widespread macrophage M1 polarization in hypervirulent Klebsiella pneumoniae-induced acute lung injury via the MSK1/p38-MAPK axis

Xu,

Zhang,

Cai

et al. 2023

Cell Mol Biol Lett

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Background Hypervirulent Klebsiella pneumoniae (hvKp) infection-induced sepsis-associated acute lung injury (ALI) has emerged as a significant clinical challenge. Increasing evidence suggests that activated inflammatory macrophages contribute to tissue damage in sepsis. However, the underlying causes of widespread macrophage activation remain unclear. Methods BALB/c mice were intravenously injected with inactivated hvKp (iHvKp) to observe lung tissue damage, inflammation, and M1 macrophage polarization. In vitro, activated RAW264.7 macrophage-derived exosomes (iHvKp-exo) were isolated and their role in ALI formation was investigated. RT-PCR was conducted to identify changes in exosomal miRNA. Bioinformatics analysis and dual-luciferase reporter assays were performed to validate MSK1 as a direct target of miR-155-5p. Further in vivo and in vitro experiments were conducted to explore the specific mechanisms involved. Results iHvKp successfully induced ALI in vivo and upregulated the expression of miR-155-5p. In vivo, injection of iHvKp-exo induced inflammatory tissue damage and macrophage M1 polarization. In vitro, iHvKp-exo was found to promote macrophage inflammatory response and M1 polarization through the activation of the p38-MAPK pathway. RT-PCR revealed exposure time-dependent increased levels of miR-155-5p in iHvKp-exo. Dual-luciferase reporter assays confirmed the functional role of miR-155-5p in mediating iHvKp-exo effects by targeting MSK1. Additionally, inhibition of miR-155-5p reduced M1 polarization of lung macrophages in vivo, resulting in decreased lung injury and inflammation induced by iHvKp-exo or iHvKp. Conclusions The aforementioned results indicate that exosomal miR-155-5p drives widespread macrophage inflammation and M1 polarization in hvKp-induced ALI through the MSK1/p38-MAPK Axis. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Exosomal miR-155-5p drives widespread macrophage M1 polarization in hypervirulent Klebsiella pneumoniae-induced acute lung injury via the MSK1/p38-MAPK axis

Xu,

Zhang,

Cai

et al. 2023

Cell Mol Biol Lett

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“…TIGIT modulates DNAM-1 mediated activation through the competitive binding of their shared ligands ( 276 ). Further, TIGIT directly inhibits DNAM-1 activation through cis interactions that interfere with DNAM-1 homodimerization ( 277 ).…”

Section: Receptor Driven Signaling In Natural Killer Cellsmentioning

confidence: 99%

Killer instincts: natural killer cells as multifactorial cancer immunotherapy

Nersesian,

Carter,

Lee

et al. 2023

Front. Immunol.

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Natural killer (NK) cells integrate heterogeneous signals for activation and inhibition using germline-encoded receptors. These receptors are stochastically co-expressed, and their concurrent engagement and signaling can adjust the sensitivity of individual cells to putative targets. Against cancers, which mutate and evolve under therapeutic and immunologic pressure, the diversity for recognition provided by NK cells may be key to comprehensive cancer control. NK cells are already being trialled as adoptive cell therapy and targets for immunotherapeutic agents. However, strategies to leverage their naturally occurring diversity and agility have not yet been developed. In this review, we discuss the receptors and signaling pathways through which signals for activation or inhibition are generated in NK cells, focusing on their roles in cancer and potential as targets for immunotherapies. Finally, we consider the impacts of receptor co-expression and the potential to engage multiple pathways of NK cell reactivity to maximize the scope and strength of antitumor activities.

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“…The recent interest in TIGIT has also been highlighted by a study showing that TIGIT-Fc recombinant protein induce sustained skin graft survival in mice via signaling through the poliovirus receptor on macrophages and inducing M2 polarization [137].…”

Section: Harnessing Inhibitory Pathways In Solid Organ Transplantationmentioning

confidence: 99%

Immune Checkpoints in Solid Organ Transplantation

Del Bello,

Treiner

2023

Biology

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Allogenic graft acceptance is only achieved by life-long immunosuppression, which comes at the cost of significant toxicity. Clinicians face the challenge of adapting the patients’ treatments over long periods to lower the risks associated with these toxicities, permanently leveraging the risk of excessive versus insufficient immunosuppression. A major goal and challenge in the field of solid organ transplantation (SOT) is to attain a state of stable immune tolerance specifically towards the grafted organ. The immune system is equipped with a set of inhibitory co-receptors known as immune checkpoints (ICs), which physiologically regulate numerous effector functions. Insufficient regulation through these ICs can lead to autoimmunity and/or immune-mediated toxicity, while excessive expression of ICs induces stable hypo-responsiveness, especially in T cells, a state sometimes referred to as exhaustion. IC blockade has emerged in the last decade as a powerful therapeutic tool against cancer. The opposite action, i.e., subverting IC for the benefit of establishing a state of specific hypo-responsiveness against auto- or allo-antigens, is still in its infancy. In this review, we will summarize the available literature on the role of ICs in SOT and the relevance of ICs with graft acceptance. We will also discuss the possible influence of current immunosuppressive medications on IC functions.

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Competitive binding of CD226/TIGIT with poliovirus receptor regulates macrophage polarization and is involved in vascularized skin graft rejection

Cited by 4 publications

References 48 publications

Exosomal miR-155-5p drives widespread macrophage M1 polarization in hypervirulent Klebsiella pneumoniae-induced acute lung injury via the MSK1/p38-MAPK axis

Exosomal miR-155-5p drives widespread macrophage M1 polarization in hypervirulent Klebsiella pneumoniae-induced acute lung injury via the MSK1/p38-MAPK axis

Killer instincts: natural killer cells as multifactorial cancer immunotherapy

Immune Checkpoints in Solid Organ Transplantation

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