Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality worldwide. There is increasing evidence that inflammation and immunological factors play an important role in the pathogenesis of VTE. Alteration of blood flow by surgery, trauma, or prolonged immobility triggers an inflammatory response, mediated by activation of multiple inflammatory pathways, and recruitment of immune cells such as neutrophils, monocytes, and platelets. These factors converge on the endothelium, changing its phenotype from antithrombotic to prothrombotic, which eventually culminates in thrombus formation. A growing number of immune system components are involved in venous thrombosis including neutrophil extracellular traps, complement pathways, inflammasomes among many others. As most immune factors are not directly involved in normal hemostasis, targeting of this pathway could efficiently prevent thrombosis while avoiding bleeding complications. Understanding the inflammatory and immunological mechanisms involved in VTE is key for developing better diagnostic, prevention, and treatment strategies.

The goal of this Research Topic is to highlight recent research that sheds light on the intricate roles that inflammation and immunity play in venous thromboembolism (VTE). We aim to publish innovative research covering this rapidly expanding area from both established leaders and emerging pioneers in the field. By compiling evidence from human translational studies, animal models, and fundamental science at the intersection of multiple disciplines, this issue seeks to accelerate advances in our collective understanding of VTE pathophysiology. Additionally, we hope to reveal promising new directions, techniques, and therapeutic strategies that may one day translate to improved patient outcomes. Overall, this issue strives to energize and empower researchers to embrace immunology and inflammation as pivotal new frontiers in the quest to better prevent, diagnose, predict, and treat VTE - the leading cause of preventable hospital death. Research in this niche domain promises clinical breakthroughs in ameliorating this disease’s substantial worldwide burden.

Research aiming at delineating immune mechanisms of VTE is ongoing globally, yet our understanding of the role of inflammation in its pathogenesis remains incomplete. The list of open research question includes, but is not limited to, the interplay between inflammation, immunological processes, immune cells, and coagulation in promoting thrombosis. Our knowledge on these key areas remains limited. The role of vascular endothelial cells in promoting localized inflammation and coagulation through expression of adhesion molecules, cytokines, and coagulation factors should be further elucidated. A better understanding of endothelial involvement may lead to new therapeutic targets. State-of the art techniques, including genomics, proteomic and single-cell sequencing approaches, are primed to identify novel inflammatory/immunological therapeutic targets in VTE. Development of novel imaging techniques to allow in vivo visualization of immune cell infiltration, endothelial dysfunction, and inflammation could significantly aid diagnosis and treatment decisions. Further, machine learning approaches can be employed to integrate clinical, genetic, immune, and coagulation biomarkers into predictive models for VTE risk stratification. Finally, the role of inflammation in chronic thrombosis resolution also remains an important facet awaiting further investigation. Filling all these gaps in knowledge would pave the way to developing more effective strategies for preventing and treating VTE.

This special issue aims to showcase high-quality original research that furthers understanding of the interplay between inflammatory and immunological pathways in the pathogenesis of VTE. We welcome submissions focusing on, but not limited to:
• Characterization of inflammatory cells, cytokines, biomarkers in VTE
• Roles of immune cell extracellular traps (NETs, EETs) in thrombosis
• Endothelial cell activation and microvascular dysfunction
• Autoantibodies, complement networks, platelets, and VTE
• Immune-coagulation protein interactions and VTE
• Influence of innate and adaptive immunity on VTE
• Role of microbiota in VTE
• Inflammation and immune system in VTE resolution
• Novel imaging tracking neuroinflammation and immunothrombosis
• Targeting inflammation and immunity for VTE prevention and treatment

Additional aspects relating immunity and inflammation to thrombosis, thrombophilia, or fibrinolysis will be considered. Translational and clinical studies in humans as well as fundamental and preclinical research are highly sought. Authors should highlight implications for better understanding VTE pathophysiology as well as future diagnostic or therapeutic innovations.

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Frontiers in Immunology

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