{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:04:42Z","timestamp":1789524282045,"version":"build-2803163510"},"reference-count":194,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA11910012"],"award-info":[{"award-number":["HDTRA11910012"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["NIH R01HL181042"],"award-info":[{"award-number":["NIH R01HL181042"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"award":["HDTRA11910012"],"award-info":[{"award-number":["HDTRA11910012"]}],"id":[{"id":"https:\/\/ror.org\/04tz64554","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NIH R01HL181042"],"award-info":[{"award-number":["NIH R01HL181042"]}],"id":[{"id":"https:\/\/ror.org\/04tz64554","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sepsis is a clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulation in immune response to infection. Dysregulated neutrophil activity plays a critical role in sepsis-induced organ failure through interactions with the vascular endothelial cells during forward and reverse migration, resulting in vascular barrier disruption and increased neutrophil trafficking into vital organs. Therapeutic approaches for treating sepsis are mainly supportive. Due to limited clinical translation from rodent models, complexity of the pathophysiology, and most importantly, the heterogenous nature of sepsis, no significant therapeutics have been successfully developed to address the underlying immune dysregulation. In this review, we will discuss the important gap in knowledge on the fundamental mechanisms of neutrophil\u2013endothelial interaction, the role that neutrophil forward and reverse migration plays in organ damage in sepsis, and how neutrophil and endothelial cell heterogeneity impact cell\u2013cell communication. We will explore emerging methodologies, including novel omic and microphysiological systems, to study the underlying mechanism of neutrophil\u2013endothelial interaction and neutrophil forward migration\/reverse migration. Finally, we will review potential therapeutic targets modulating neutrophil\u2013endothelial interaction and the challenges of translating them from bench to bedside.<\/jats:p>","DOI":"10.3390\/cells15070581","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:05:33Z","timestamp":1774451133000},"page":"581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dysregulation of Neutrophil\u2013Endothelial Communication in Sepsis: Mechanisms and Therapeutic Perspectives"],"prefix":"10.3390","volume":"15","author":[{"given":"Nazgol","family":"Esmalian Afyouni","sequence":"first","affiliation":[{"name":"Center for Inflammation and Lung Research, Department of Microbiology, Immunology and Inflammation, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad F.","family":"Kiani","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Temple University, Philadelphia, PA 19122, USA"},{"name":"Department of Radiation Oncology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2554-507X","authenticated-orcid":false,"given":"Laurie E.","family":"Kilpatrick","sequence":"additional","affiliation":[{"name":"Center for Inflammation and Lung Research, Department of Microbiology, Immunology and Inflammation, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3390\/epidemiologia5030032","article-title":"The Global Burden of Sepsis and Septic Shock","volume":"5","author":"Sangiorgio","year":"2024","journal-title":"Epidemiologia"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Morrissey, R., Lee, J., Baral, N., Tauseef, A., Sood, A., Mirza, M., and Jabbar, A.B.A. (2025). 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