PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway

Li, Yulong; Xin, Guang; Li, Shiyi; Dong, Yuman; Zhu, Yuda; Yu, Xiuxian; Wan, Chengyu; Li, Fan; Wei, Zeliang; Wang, Yilan; Zhang, Kun; Chen, Qingqiu; Niu, Hai; Huang, Wen

doi:10.3389/fphar.2022.921414

Cited by 6 publications

(2 citation statements)

References 62 publications

(72 reference statements)

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“…The cancer cells can activate the coagulation cascade and other prothrombotic processes in the host cell in absence of other predisposing factors for thrombosis. activation and arterial thrombosis [4], but several studies did not found a relationship between the presence of PD-L1 mutation and venous thrombosis [5,6].…”

Section: Discussionmentioning

confidence: 99%

Case Report OCLC Number/Unique Identifier: Unusual Thrombosis Despite Anticoagulation

Tiron

2022

J Biomed Res Environ Sci

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Background: Pulmonary Embolism (PE) is a life-threatening condition with annual incidence ranging from 39 to 115 cases per 100,000 population [1]. Along with many other causes, neoplasia is one of the highest risk factors for pancreatic, lung, gastric, cerebral and haematological cancer [2]. Patients with neoplasia often have venous thromboembolism (VTE) during the course of the disease, but occasionally neoplasia is diagnosed as secondary to VTE. Case Presentation: A 55-year-old man known with high blood pressure and dyslipidaemia is diagnosed with bilateral distal Deep Venous Thrombosis (DVT) and treated with a factor Xa inhibitor. Two months later he is admitted for fatigue, dry cough, unwanted weight loss of approximately 5kg for a month and progressive exertion dyspnea. The echocardiographic examination reveals dilated right chambers with thrombus in the Right Ventricle (RV). The suspicion of pulmonary embolism it was confirmed on thoracic contrast CT examination. Large bilateral mediastinal adenopathies and a right lung nodule were also visualised on lung CT scan. The patient was treated with unfractionated heparin, slow-acting nitrate, aspirin, calcium blocker, with the disappearance of the thrombus from the right ventricle. Bronchoscopy showed a lesion near the right main bronchus. The diagnosis of pulmonary adenocarcinoma is confirmed histopathologically on the sample obtained at bronchoscopy and from the mediastinal lymph node obtained at mediastinoscopy. The patient was referred to the oncology service for specialised treatment. Conclusion: VTE under anticoagulant treatment should always raise some suspicions and other causes should be sought. Undiagnosed neoplasms , drug resistance or drug interactions, thrombophilias are some of the causes that should be suspected in case of thrombosis under therapeutic anticoagulant.

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Section: Discussionmentioning

confidence: 99%

Case Report OCLC Number/Unique Identifier: Unusual Thrombosis Despite Anticoagulation

Tiron

2022

J Biomed Res Environ Sci

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“…NLRP3 affected platelet αIIbβ3 outside-in signal transduction, an essential process for hemostasis and thrombosis, which might be mediated by IL-1β, as significantly reduced IL-1β release was found in NLRP3-deficient platelets ( 96 ). Furthermore, in thrombin activated-platelets, the caspase-3/GSDME pathway was upregulated, further regulating platelet integrin αIIbβ3 activation ( 97 ).…”

Section: Pyroptosis-induced Hemostasis Activation In Sepsismentioning

confidence: 99%

Role of pyroptosis in hemostasis activation in sepsis

et al. 2023

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Sepsis is frequently associated with hemostasis activation and thrombus formation, and systematic hemostatic changes are associated with a higher risk of mortality. The key events underlying hemostasis activation during sepsis are the strong activation of innate immune pathways and the excessive inflammatory response triggered by invading pathogens. Pyroptosis is a proinflammatory form of programmed cell death, that defends against pathogens during sepsis. However, excessive pyroptosis can lead to a dysregulation of host immune responses and organ dysfunction. Recently, pyroptosis has been demonstrated to play a prominent role in hemostasis activation in sepsis. Several studies have demonstrated that pyroptosis participates in the release and coagulation activity of tissue factors. In addition, pyroptosis activates leukocytes, endothelial cells, platelets, which cooperate with the coagulation cascade, leading to hemostasis activation in sepsis. This review article attempts to interpret the molecular and cellular mechanisms of the hemostatic imbalance induced by pyroptosis during sepsis and discusses potential therapeutic strategies.

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Extracellular vesicles recovered from plasma of severe dengue patients induce CD4+ T cell suppression through PD-L1/PD-1 interaction

Kumari,

Bandyopadhyay,

Singh

et al. 2023

mBio

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Extracellular vesicles (EVs) are small membrane vesicles secreted into biological fluids, which play crucial roles in influencing the cellular function in different pathological processes. However, there is less clarity on how plasma EVs influence proliferation activation and functions of immune cells during dengue virus (DV) infection. In this study, we aimed to characterize circulating EVs from different categories of dengue patients and examined the consequence of naïve CD4+ T cells to EVs isolated from the plasma of mild or severe dengue patients. We observed that severe dengue infection was associated with an increased release of CD41a+ platelet extracellular vesicles compared with that from patients with mild disease or healthy donors. These EVs carried an increased level of pro- and anti-inflammatory cytokines along with immunoregulatory proteins on the surface that caused CD4+ T cell suppression. Treatment of purified naïve CD4+ T cells with EVs derived from severe dengue plasma drove CD4+ proliferation toward specific subtypes and modulated surface receptor CXCR3 and CCR6 expression. Subsequent studies indicated a notable rise in programmed cell death ligand 1 (PD-L1) expression within CD41a+ severe DV (SDV) EVs. Additionally, CD4+ T cells showed an elevated increase in programmed cell death 1 (PD-1) after incubating with SDV-EVs. We also demonstrated that blocking PD-L1 on SDV-EVs or PD-1 on late-activating CD4 + T cells partially reversed the SDV-EV-induced suppression of CD4+ T cell proliferation. Overall, our study highlights the immunosuppressive property of EVs derived from plasma of severe dengue patients, which might contribute to immune pathogenesis by shaping the immune response. IMPORTANCE Severe dengue manifestations caused by the dengue virus are a global health problem. Studies suggest that severe dengue disease depends on uncontrolled immune cell activation, and excessive inflammation adds to the pathogenesis of severe dengue disease. Therefore, it is important to understand the process that triggers the uncontrolled activation of the immune cells. The change in immune response in mild to severe dengue may be due to direct virus-to-cell interaction or it could be a contact-independent process through the extracellular vesicles (EVs) released from infected cells. The importance of circulating EVs in the context of dengue virus infection and pathogenesis remains unexplored. Therefore, understanding the possible biological function of circulating EVs may help to delineate the role of EVs in the progression of disease. Our present study highlights that EVs from plasma of severe dengue patients can have immunosuppressive properties on CD4+ T cells which may contribute to T cell suppression and may contribute to dengue disease progression.

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PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway

Cited by 6 publications

References 62 publications

Case Report OCLC Number/Unique Identifier: Unusual Thrombosis Despite Anticoagulation

Case Report OCLC Number/Unique Identifier: Unusual Thrombosis Despite Anticoagulation

Role of pyroptosis in hemostasis activation in sepsis

Extracellular vesicles recovered from plasma of severe dengue patients induce CD4+ T cell suppression through PD-L1/PD-1 interaction

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