Evidence of interplay between thrombosis and inflammation in various pathophysiological situations such as disseminated intravascular coagulation, stroke, cancer and rheumatoid arthritis has led to the concept of thromboinflammation. Thromboinflammation is driven by mutual interactions and reciprocal activation between endothelial cells, leukocytes, platelets, and the humoral innate immune system, involving the complement, coagulation, and fibrinolytic signaling cascades.

It is well known that both arterial and venous thrombosis can occur in the absence of vascular damage. This suggests that in addition to the exposed sub-endothelium, activated endothelial cells and leukocytes are also involved in the regulation of thromboinflammation, notably in cases such as reduced blood flow, stasis, or infection. In the case of infection, thromboinflammation triggered by the innate immune system can play a physiological role and provide a first line of defense to control infection, a process known as immuno-thrombosis.

Despite being small and anucleated, platelets can exert both hemostatic and immune effector responses. It is well recognized that platelets are equipped with a broad variety of receptors and molecules that allow the continuous surveillance of any potential danger signal, including vascular injury but also sterile, infectious or autologous insult. Moreover, platelets not only recognize the danger signal and react to halt it, but also, when necessary, communicate with immune and endothelial cells to guarantee an effective immune response to maintain homeostasis. For instance, IL-1 in the platelet microparticles has been shown to prompt immune cells within the joints to secrete pro-inflammatory molecules. Additionally, platelets interact with various types of leukocytes to deal with both infectious and sterile stimuli. Recent evidence supports the notion that independently of platelet plug formation, platelets exert immune and inflammatory functions (e.g. regulation of endothelial permeability and leukocyte recruitment), while continuously securing the inflamed vasculature and preventing bleeding from the very onset of inflammation.

A better understanding of the intimate and overlapping activities of blood cells, endothelium and coagulation proteins during inflammation/infection is critical for the development of new therapies for infectious diseases, cardiovascular and regenerative medicine. Moreover, application of therapies targeting thromboinflammation could be beneficial in preventing tissue loss due to clotting and in increasing the efficacy of immune cell therapies against diseases such as diabetes mellitus, liver insufficiency, and graft-versus-host disease.

In this Research Topic, we welcome the submission of Original Research Articles, Reviews and Commentaries that shed light on novel information regarding the interplay between platelets, immune cells and vascular cells in thromboinflammation during homeostasis and disease. We suggest the following subtopics:

1. Role of platelets in thromboinflammation
2. Interplay between platelets and innate immune cells in thromboinflammation
3. Role of humoral immune responses in thromboinflammation
4. Role of T Cells in thromboinflammation
5. Role of platelets in cytokine-mediated immune responses
6. Model systems to study thromboinflammation
7. Implications of thromboinflammation in immune-mediated diseases and cancer

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