{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:51:49Z","timestamp":1789487509140,"version":"build-2803163510"},"reference-count":218,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Sepsis is a life-threatening organ dysfunction that is caused by a dysregulated host response to infection; moreover, multiple organ failure is a major contributor to mortality. Immunothrombosis, which is driven by the coordinated activation of innate immunity and coagulation within the microvasculature, links systemic inflammation to microvascular dysfunction and organ injury. In this review, we utilize a microvascular architecture-centered framework to explain how a systemically triggered immunothrombotic response gives rise to distinct patterns of organ injury. We summarize the major mechanisms of sepsis-induced immunothrombosis, including endothelial dysfunction, platelet\u2013neutrophil interactions, complement activation, and monocyte\/macrophage-derived tissue factor expression. We further examine the differences in endothelial phenotype, barrier specialization, flow dynamics, resident immune niches, and oxygen supply\u2013demand balance that shape injury patterns in the lungs, kidneys, heart, liver, brain, and intestines. We also discuss the diagnostic considerations and therapeutic strategies related to sepsis-induced immunothrombosis, while focusing on coagulation assessment, microcirculatory dysfunction, and the limitations of current anti-thromboinflammatory interventions. Finally, we highlight the unresolved challenge of distinguishing protective immunothrombosis from pathological thromboinflammatory injury, which may inform future efforts to improve patient stratification and risk\u2013benefit assessments.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1919351","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T14:24:25Z","timestamp":1789482265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sepsis-induced immunothrombosis: from cellular crosstalk to multiple organ dysfunction"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiyuan","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency and 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