{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:53:33Z","timestamp":1791219213908,"version":"4.1.0"},"reference-count":110,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T00:00:00Z","timestamp":1747526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Inflammatory bowel disease (IBD) is a growing global problem, particularly in regions with low sociodemographic indices and growing populations. IBD incidence is increasing among children and adolescents, leading to a growing economic burden. The prevalence of atherosclerotic cardiovascular diseases among patients with IBD is also higher than in the general population. While mortality rates have decreased, cardiovascular disease (CVD) remains a significant contributor to mortality and disability in IBD patients. According to the current understanding, neutrophils play an important role in both the atherogenesis and pathogenesis of IBD. This review addresses the state of the art of neutrophil involvement in the development of atherosclerosis and IBD. In the present review, we summarize the currently available evidence regarding neutrophils as a possible key driver of extraintestinal manifestations of IBD and cardiovascular complications. We provide a discussion on the potential role of neutrophil-derived markers in the development of new approaches for the precise diagnosis of atherosclerosis in patients with IBD, as well as new therapeutic targets.<\/jats:p>","DOI":"10.3390\/cells14100738","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:54:28Z","timestamp":1747724068000},"page":"738","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Neutrophils at the Crossroads of Inflammatory Bowel Disease and Atherosclerosis: A State-of-the-Art Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5902-3803","authenticated-orcid":false,"given":"Vadim","family":"Genkel","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, South-Ural State Medical University, Chelyabinsk 454141, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7039-838X","authenticated-orcid":false,"given":"Yana","family":"Zaripova","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, South-Ural State Medical University, Chelyabinsk 454141, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla","family":"Kuznetsova","sequence":"additional","affiliation":[{"name":"Department of Hospital Therapy, South-Ural State Medical University, Chelyabinsk 454141, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3323-9854","authenticated-orcid":false,"given":"Alena","family":"Sluchanko","sequence":"additional","affiliation":[{"name":"Department of Hospital Therapy, South-Ural State Medical University, Chelyabinsk 454141, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Minasova","sequence":"additional","affiliation":[{"name":"Research Institution of Immunology, South-Ural State Medical University, Chelyabinsk 454141, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Zotova","sequence":"additional","affiliation":[{"name":"Research Institution of Immunology, South-Ural State Medical University, Chelyabinsk 454141, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3481-8092","authenticated-orcid":false,"given":"Anna","family":"Saenko","sequence":"additional","affiliation":[{"name":"Department of Hospital Therapy, South-Ural State Medical University, Chelyabinsk 454141, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albina","family":"Savochkina","sequence":"additional","affiliation":[{"name":"Research Institution of Immunology, South-Ural State Medical University, Chelyabinsk 454141, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiya","family":"Dolgushina","sequence":"additional","affiliation":[{"name":"Department of Hospital Therapy, South-Ural State Medical University, Chelyabinsk 454141, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhou, J.L., Bao, J.C., Liao, X.Y., Chen, Y.J., Wang, L.W., Fan, Y.Y., Xu, Q.Y., Hao, L.X., Li, K.J., and Liang, M.X. (2023). Trends and projections of inflammatory bowel disease at the global, regional and national levels, 1990\u20132050: A Bayesian age-period-cohort modeling study. BMC Public Health, 23.","DOI":"10.1186\/s12889-023-17431-8"},{"key":"ref_2","first-page":"izad295","article-title":"The epidemiology of inflammatory bowel disease in Oceania: A systematic review and meta-analysis of incidence and prevalence","volume":"30","author":"Forbes","year":"2023","journal-title":"Inflamm. Bowel. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103498","DOI":"10.1016\/j.autrev.2023.103498","article-title":"Global, regional, and national burden of inflammatory bowel disease and its associated anemia, 1990 to 2019 and predictions to 2050: An analysis of the global burden of disease study 2019","volume":"23","author":"Wang","year":"2023","journal-title":"Autoimmun. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"04174","DOI":"10.7189\/jogh.13.04174","article-title":"Epidemiological analysis reveals a surge in inflammatory bowel disease among children and adolescents: A global, regional, and national perspective from 1990 to 2019\u2013insights from the China study","volume":"13","author":"Zhang","year":"2023","journal-title":"J. Glob. Health"},{"key":"ref_5","first-page":"izad302","article-title":"Sustained increase in pediatric inflammatory bowel disease incidence across the South West United Kingdom over the last 10 years","volume":"19","author":"Green","year":"2024","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00011-023-01836-7","article-title":"Global evolving patterns and cross-country inequalities of inflammatory bowel disease burden from 1990 to 2019: A worldwide report","volume":"73","author":"Cao","year":"2024","journal-title":"Inflamm. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1080\/08998280.2021.1919009","article-title":"Trends in hospitalizations and mortality for inflammatory bowel disease from a nationwide database study between 2008 and 2018","volume":"34","author":"Kichloo","year":"2021","journal-title":"Bayl. Univ. Med Cent. Proc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s44197-023-00145-w","article-title":"Evolving trends and burden of inflammatory bowel disease in Asia, 1990\u20132019: A comprehensive analysis based on the Global Burden of Disease Study","volume":"13","author":"Chen","year":"2023","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/ecco-jcc\/jjac166","article-title":"Increased risk of cancer and mortality in a large French population-based paediatric-onset inflammatory bowel disease retrospective cohort","volume":"17","author":"Leroyer","year":"2023","journal-title":"J. Crohns Colitis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/ecco-jcc\/jjac156","article-title":"Mortality in patients with inflammatory bowel disease: Results from 30 years of follow-up in a Norwegian inception cohort (the IBSEN study)","volume":"17","author":"Hovde","year":"2023","journal-title":"J. Crohns Colitis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/RHU.0000000000001818","article-title":"Proportionate cardiovascular mortality in chronic inflammatory disease in adults in the United States from 1999 to 2019","volume":"28","author":"Shah","year":"2022","journal-title":"J. Clin. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e32775","DOI":"10.1097\/MD.0000000000032775","article-title":"Inflammatory bowel disease and associated cardiovascular disease outcomes: A systematic review","volume":"102","author":"Jaiswal","year":"2023","journal-title":"Medicine"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Groenendyk, J.W., Rivera, A.S., Sinha, A., Lloyd-Jones, D.M., and Feinstein, M.J. (2021). Changes in proportionate cardiovascular mortality in patients with chronic infectious and inflammatory conditions in the United States, 1999\u20132018. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-03407-4"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17562848211032126","DOI":"10.1177\/17562848211032126","article-title":"Thromboembolic and atherosclerotic cardiovascular events in inflammatory bowel disease: Epidemiology, pathogenesis, and clinical management","volume":"14","author":"Sleutjes","year":"2021","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1177\/2047487318792952","article-title":"Inflammatory bowel disease and cardiovascular disease incidence and mortality: A meta-analysis","volume":"25","author":"Sun","year":"2018","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100316","DOI":"10.1016\/j.ajpc.2022.100316","article-title":"Inflammatory bowel disease and atherosclerotic cardiovascular disease in U.S. adults\u2014A population-level analysis in the National Health Interview Survey","volume":"9","author":"Nasir","year":"2022","journal-title":"Am. J. Prev. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.amjmed.2021.02.029","article-title":"Premature atherosclerotic cardiovascular disease risk among patients with inflammatory bowel disease","volume":"134","author":"Lee","year":"2021","journal-title":"Am. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.cgh.2022.08.035","article-title":"Inflammatory bowel disease is associated with an increased risk of incident acute arterial events: Analysis of the United Kingdom Biobank","volume":"21","author":"Alayo","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1093\/ibd\/izab326","article-title":"Risks of cardiovascular events in patients with inflammatory bowel disease in China: A retrospective multicenter cohort study","volume":"28","author":"Fang","year":"2022","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Livzan, M.A., Bikbavova, G.R., Lisyutenko, N.S., Romanyuk, A.E., and Drapkina, O.M. (2024). Cardiovascular Risk in Patients with Inflammatory Bowel Diseases-The Role of Endothelial Dysfunction. Diagnostics, 14.","DOI":"10.3390\/diagnostics14161722"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1093\/eurjpc\/zwac110","article-title":"Prevalence of ideal cardiovascular health and its correlates in patients with inflammatory bowel disease, psoriasis and spondyloarthropathy","volume":"29","author":"Sleutjes","year":"2022","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100171","DOI":"10.1016\/j.ajpc.2021.100171","article-title":"Prevalence of cardiovascular risk factors in a nationally representative adult population with inflammatory bowel disease without atherosclerotic cardiovascular disease","volume":"16","author":"Agrawal","year":"2021","journal-title":"Am. J. Prev. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3390\/gastroent15040067","article-title":"Too Many Couch Potatoes Among Middle-Aged Inflammatory Bowel Disease Patients: Findings from the \u201cBE-FIT-IBD-2\u201d Study","volume":"15","author":"Gravina","year":"2024","journal-title":"Gastroenterol. Insights"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5668","DOI":"10.3748\/wjg.v29.i41.5668","article-title":"Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity: The \u201cBE-FIT-IBD\u201d study","volume":"29","author":"Gravina","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kaazan, P., Seow, W., Yong, S., Heilbronn, L.K., and Segal, J.P. (2023). The Impact of Obesity on Inflammatory Bowel Disease. Biomedicines, 11.","DOI":"10.3390\/biomedicines11123256"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s11894-022-00840-x","article-title":"Impact of Obesity on Inflammatory Bowel Disease","volume":"24","author":"Khakoo","year":"2022","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.3748\/wjg.v30.i9.1132","article-title":"Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients: A matter of disease activity?","volume":"30","author":"Gravina","year":"2024","journal-title":"World J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1038\/s41467-025-56936-1","article-title":"Melanocortin 3 receptor regulates hepatic autophagy and systemic adiposity","volume":"16","author":"Patel","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1530\/JOE-17-0636","article-title":"Melanocortin overexpression limits diet-induced inflammation and atherosclerosis in LDLR-\/- mice","volume":"236","author":"Nuutinen","year":"2018","journal-title":"J. Endocrinol."},{"key":"ref_30","first-page":"502314","article-title":"Spanish Working Group in Crohn\u2019s Disease and Ulcerative Colitis (GETECCU) position paper on cardiovascular disease in patients with inflammatory bowel disease","volume":"48","author":"Carpio","year":"2025","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Camba, A., Carrillo-Palau, M., Ramos, L., Hern\u00e1ndez Alvarez-Buylla, N., Alonso-Abreu, I., Hern\u00e1ndez-P\u00e9rez, A., Vela, M., Arranz, L., Hern\u00e1ndez-Guerra, M., and Gonz\u00e1lez-Gay, M.\u00c1. (2021). Carotid plaque assessment reclassifies patients with inflammatory bowel disease into very-high cardiovascular risk. J. Clin. Med., 10.","DOI":"10.3390\/jcm10081671"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ahj.2023.08.011","article-title":"Coronary artery calcium scoring for cardiovascular risk assessment in patients with inflammatory bowel disease","volume":"266","author":"Naami","year":"2023","journal-title":"Am. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"495","DOI":"10.5217\/ir.2022.00017","article-title":"Abdominal aortic calcification in patients with inflammatory bowel disease: Does anti-tumor necrosis factor \u03b1 use protect from chronic inflammation-induced atherosclerosis?","volume":"20","author":"Mantaka","year":"2022","journal-title":"Intestig. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1093\/eurjpc\/zwad124","article-title":"Cardiovascular risk profiles in patients with inflammatory bowel disease differ from matched controls from the general population","volume":"30","author":"Sleutjes","year":"2023","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_35","first-page":"izae007","article-title":"Performance of ASCVD risk prediction models in individuals with inflammatory bowel disease: A UK Biobank study","volume":"18","author":"Alayo","year":"2024","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41569-019-0326-7","article-title":"Neutrophils as regulators of cardiovascular inflammation","volume":"17","author":"Braster","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-pathmechdis-051222-015009","article-title":"Neutrophils in physiology and pathology","volume":"19","author":"Vicanolo","year":"2024","journal-title":"Annu. Rev. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Garratt, L.W. (2021). Current understanding of the neutrophil transcriptome in health and disease. Cells, 10.","DOI":"10.3390\/cells10092406"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1038\/s41467-021-22973-9","article-title":"The neutrotime transcriptional signature defines a single continuum of neutrophils across biological compartments","volume":"12","author":"Radtke","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1038\/s41590-020-0736-z","article-title":"Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection","volume":"21","author":"Xie","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.jacc.2016.12.022","article-title":"Neutrophil counts and initial presentation of 12 cardiovascular diseases: A CALIBER cohort study","volume":"69","author":"Shah","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1161\/ATVBAHA.118.310945","article-title":"Association of total and differential leukocyte counts with cardiovascular disease and mortality in the UK Biobank","volume":"38","author":"Welsh","year":"2018","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4953","DOI":"10.1093\/eurheartj\/ehad649","article-title":"Neutrophil counts and cardiovascular disease","volume":"44","author":"Luo","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4965","DOI":"10.1093\/eurheartj\/ehad711","article-title":"Beyond association: High neutrophil counts are a causal risk factor for atherosclerotic cardiovascular disease","volume":"44","author":"Soehnlein","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/17534259231189195","article-title":"Role of neutrophils in different stages of atherosclerosis","volume":"29","author":"Zhang","year":"2023","journal-title":"Innate Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1093\/cvr\/cvab302","article-title":"Neutrophils in cardiovascular disease: Warmongers, peacemakers, or both?","volume":"118","author":"Sreejit","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/s41423-021-00832-3","article-title":"Neutrophils in chronic inflammatory diseases","volume":"19","author":"Soehnlein","year":"2022","journal-title":"Cell Mol. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e12952","DOI":"10.1111\/eci.12952","article-title":"Cytokine production by human neutrophils: Revisiting the \u201cdark side of the moon\u201d","volume":"48","author":"Tamassia","year":"2018","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.jcmgh.2017.07.001","article-title":"Neutrophils as components of mucosal homeostasis","volume":"4","author":"Hall","year":"2017","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s41575-023-00871-3","article-title":"Neutrophils: From IBD to the gut microbiota","volume":"21","author":"Danne","year":"2024","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1053\/j.gastro.2022.05.029","article-title":"Neutralizing anti-granulocyte macrophage-colony stimulating factor autoantibodies recognize post-translational glycosylations on granulocyte macrophage-colony stimulating factor years before diagnosis and predict complicated Crohn\u2019s disease","volume":"163","author":"Mortha","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Saez, A., Herrero-Fernandez, B., Gomez-Bris, R., Sanchez-Martinez, H., and Gonzalez-Granado, J.M. (2023). Pathophysiology of inflammatory bowel disease: Innate immune system. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021526"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e12983","DOI":"10.1111\/eci.12983","article-title":"The role of neutrophils in the pathogenesis of Crohn\u2019s disease","volume":"48","author":"Segal","year":"2018","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1093\/ibd\/izy265","article-title":"Genetic and transcriptomic variation linked to neutrophil granulocyte-macrophage colony-stimulating factor signaling in pediatric Crohn\u2019s disease","volume":"25","author":"Denson","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1080\/17474124.2022.2100759","article-title":"Targeting neutrophils in inflammatory bowel disease: Revisiting the role of adsorptive granulocyte and monocyte apheresis","volume":"16","author":"Bamias","year":"2022","journal-title":"Expert. Rev. Gastroenterol. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1093\/ecco-jcc\/jjad110","article-title":"Neutrophil-only histological assessment of ulcerative colitis correlates with endoscopic activity and predicts long-term outcomes in a multicentre study","volume":"17","author":"Parigi","year":"2023","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1016\/j.cgh.2019.12.011","article-title":"Complete resolution of mucosal neutrophils associates with improved long-term clinical outcomes of patients with ulcerative colitis","volume":"18","author":"Pai","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zhang, C., Zhang, J., Zhang, Y., Song, Z., Bian, J., Yi, H., and Ma, Z. (2023). Identifying neutrophil-associated subtypes in ulcerative colitis and confirming neutrophils promote colitis-associated colorectal cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1095098"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"17562848231155987","DOI":"10.1177\/17562848231155987","article-title":"Pursuing neutrophils: Systematic scoping review on blood-based biomarkers as predictors of treatment outcomes in inflammatory bowel disease","volume":"16","author":"Estevinho","year":"2023","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1093\/ecco-jcc\/jjac003","article-title":"Detailed transcriptional landscape of peripheral blood points to increased neutrophil activation in treatment-na\u00efve inflammatory bowel disease","volume":"16","author":"Juzenas","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"van Unen, V., Ouboter, L.F., Li, N., Schreurs, M., Abdelaal, T., Kooy-Winkelaar, Y., Beyrend, G., H\u00f6llt, T., Maljaars, P.W.J., and Mearin, M.L. (2022). Identification of a disease-associated network of intestinal immune cells in treatment-na\u00efve inflammatory bowel disease. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.893803"},{"key":"ref_62","first-page":"402","article-title":"The emerging role of neutrophils in autoimmune-associated disorders: Effector, predictor, and therapeutic targets","volume":"2","author":"Fu","year":"2021","journal-title":"Med. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41577-022-00787-0","article-title":"Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases","volume":"23","author":"Wigerblad","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1093\/cei\/uxac093","article-title":"Neutrophils in autoimmunity: When the hero becomes the villain","volume":"210","author":"Bissenova","year":"2022","journal-title":"Clin. Exp. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"109843","DOI":"10.1016\/j.intimp.2023.109843","article-title":"Neutrophil extracellular trap: A key player in the pathogenesis of autoimmune diseases","volume":"116","author":"Sadeghi","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Xu, G., Zhang, W., Yang, J., Sun, N., and Qu, X. (2023). Identification of neutrophil extracellular traps and crosstalk genes linking inflammatory bowel disease and osteoporosis by integrated bioinformatics analysis and machine learning. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-50488-4"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ding, Y., Yang, Y., and Xue, L. (2023). Immune cells and their related genes provide a new perspective on the common pathogenesis of ankylosing spondylitis and inflammatory bowel diseases. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1137523"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Jatana, S., Ponti, A.K., Johnson, E.E., Rebert, N.A., Smith, J.L., Fulmer, C.G., Maytin, E.V., Achkar, J.P., Fernandez, A.P., and McDonald, C. (2023). A novel murine model of pyoderma gangrenosum reveals that inflammatory skin-gut crosstalk is mediated by IL-1\u03b2-primed neutrophils. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1148893"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"He, R., Zhao, S., Cui, M., Chen, Y., Ma, J., Li, J., and Wang, X. (2023). Cutaneous manifestations of inflammatory bowel disease: Basic characteristics, therapy, and potential pathophysiological associations. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1234535"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s41232-023-00257-7","article-title":"Increased neutrophils in inflammatory bowel disease accelerate the accumulation of amyloid plaques in the mouse model of Alzheimer\u2019s disease","volume":"43","author":"Kaneko","year":"2023","journal-title":"Inflamm. Regen."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.5551\/jat.62970","article-title":"Associations of baseline and changes in leukocyte counts with incident cardiovascular events: The Dongfeng-Tongji Cohort Study","volume":"29","author":"Wang","year":"2022","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.5551\/jat.63887","article-title":"Distinct WBC trajectories are associated with the risks of incident CVD and all-cause mortality","volume":"30","author":"Yang","year":"2023","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Feng, W., Liu, Y., Zhu, L., Xu, L., and Shen, H. (2022). Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential markers for ulcerative colitis: A retrospective study. BMC Gastroenterol., 22.","DOI":"10.1186\/s12876-022-02571-9"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kurimoto, N., Nishida, Y., Hosomi, S., Itani, S., Kobayashi, Y., Nakata, R., \u014cminami, M., Nadatani, Y., Fukunaga, S., and \u014ctani, K. (2023). Neutrophil-to-lymphocyte ratio may predict clinical relapse in ulcerative colitis patients with mucosal healing. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0280252"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.2147\/JIR.S423086","article-title":"Serological biomarker-based machine learning models for predicting the relapse of ulcerative colitis","volume":"16","author":"Pang","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/1751-2980.12540","article-title":"Potential roles of neutrophils in regulating intestinal mucosal inflammation of inflammatory bowel disease","volume":"18","author":"Zhou","year":"2017","journal-title":"J. Dig. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"113934","DOI":"10.1016\/j.celrep.2024.113934","article-title":"Wnt5 controls splenic myelopoiesis and neutrophil functional ambivalency during DSS-induced colitis","volume":"43","author":"Luan","year":"2024","journal-title":"Cell Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"112637","DOI":"10.1016\/j.celrep.2023.112637","article-title":"IL-3 orchestrates ulcerative colitis pathogenesis by controlling the development and the recruitment of splenic reservoir neutrophils","volume":"42","author":"Glanz","year":"2023","journal-title":"Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3390\/gidisord4040025","article-title":"Neutrophils in intestinal inflammation: What we know and what we could expect for the near future","volume":"4","author":"Arosa","year":"2022","journal-title":"Gastrointest. Disord."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/j.jacc.2019.07.061","article-title":"From focal lipid storage to systemic inflammation: JACC Review Topic of the Week","volume":"74","author":"Libby","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ostendorf, Y., Rolauer, L., Pasch, N., Schaefer, H., Heitmann, S., Petzsch, P., Poschmann, G., Hartwig, S., Lehr, S., and Koehrer, K. (2022). Neutrophils as major drivers of increased atherosclerosis in a murine model of chronic colitis. Eur. Heart J., 43.","DOI":"10.1093\/eurheartj\/ehac544.3042"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Yao, Z., Zhang, B., Niu, G., Yan, Z., Tong, X., Zou, Y., Li, Y., and Yang, M. (2022). Neutrophil infiltration characterized by upregulation of S100A8, S100A9, S100A12, and CXCR2 is associated with the co-occurrence of Crohn\u2019s disease and peripheral artery disease. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.896645"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e18175","DOI":"10.1111\/jcmm.18175","article-title":"Identification of key biomarkers for predicting CAD progression in inflammatory bowel disease via machine-learning and bioinformatics strategies","volume":"28","author":"Tang","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Luo, X., Wang, R., Zhang, X., Wen, X., Deng, S., and Xie, W. (2023). Identification of CCL2, CXCR2, S100A9 as immune-related gene markers and immune infiltration characteristics of inflammatory bowel disease and heart failure via bioinformatics analysis and machine learning. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1268675"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Fu, Q., Shen, T., Qiu, W., Liao, Y., Yu, M., and Zhou, Y. (2025). FOSB is a key factor in the genetic link between inflammatory bowel disease and acute myocardial infarction: Multiple bioinformatics analyses and validation. BMC Med. Genom., 18.","DOI":"10.1186\/s12920-025-02129-0"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Wu, M., Liu, D., Xiong, X., Su, Q., Xiang, Y., Shen, L., An, Z., and Yang, X. (2025). Analysis of the molecular mechanisms of ulcerative colitis and atherosclerosis by microarray data. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-95125-4"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Buso, G., Faggin, E., Bressan, A., Galliazzo, S., Cinetto, F., Felice, C., Fusaro, M., Erdmann, A., Pauletto, P., and Rattazzi, M. (2023). Biomarkers of neutrophil activation in patients with symptomatic chronic peripheral artery disease predict worse cardiovascular outcome. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030866"},{"key":"ref_88","first-page":"izae032","article-title":"Comparison of fecal calprotectin and myeloperoxidase in predicting outcomes in inflammatory bowel disease","volume":"28","author":"Swaminathan","year":"2024","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e00605","DOI":"10.14309\/ctg.0000000000000605","article-title":"Fecal biomarkers of neutrophil and eosinophil origin reflect the response to biological therapy and corticosteroids in patients with inflammatory bowel disease","volume":"14","author":"Peterson","year":"2023","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5820","DOI":"10.1038\/s41467-022-33331-8","article-title":"Interleukin-22 regulates neutrophil recruitment in ulcerative colitis and is associated with resistance to ustekinumab therapy","volume":"13","author":"Pavlidis","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Zhou, Z., Zhang, Y., Yang, X., Pan, Y., Li, L., Gao, C., and He, C. (2022). Clinical significance of novel neutrophil-based biomarkers in the diagnosis and prediction of response to infliximab therapy in Crohn\u2019s disease. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.865968"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1038\/s41591-021-01520-5","article-title":"IL-1-driven stromal-neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies","volume":"27","author":"Friedrich","year":"2021","journal-title":"Nat. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1016\/j.jacc.2020.08.011","article-title":"Inhibition of interleukin-1\u03b2 and reduction in atherothrombotic cardiovascular events in the CANTOS trial","volume":"76","author":"Everett","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Aggeletopoulou, I., Kalafateli, M., Tsounis, E.P., and Triantos, C. (2024). Exploring the role of IL-1\u03b2 in inflammatory bowel disease pathogenesis. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1307394"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"otae003","DOI":"10.1093\/crocol\/otae003","article-title":"Formylated peptide receptor-1-mediated gut inflammation as a therapeutic target in inflammatory bowel disease","volume":"6","author":"McAllister","year":"2024","journal-title":"Crohns Colitis 360"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"108257","DOI":"10.1016\/j.pharmthera.2022.108257","article-title":"Targeting CXCR1 and CXCR2 receptors in cardiovascular diseases","volume":"237","author":"Dhayni","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"115175","DOI":"10.1016\/j.ejmech.2023.115175","article-title":"Expanding role of CXCR2 and therapeutic potential of CXCR2 antagonists in inflammatory diseases and cancers","volume":"250","author":"Xie","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1096\/fj.201902542R","article-title":"Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b\/CD18","volume":"34","author":"Kelm","year":"2020","journal-title":"FASEB J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e22967","DOI":"10.1096\/fj.202201995RR","article-title":"PTK2B regulates immune responses of neutrophils and protects mucosal inflammation in ulcerative colitis","volume":"37","author":"Zhou","year":"2023","journal-title":"FASEB J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1177\/15353702231184217","article-title":"Neutrophil extracellular traps contributing to atherosclerosis: From pathophysiology to clinical implications","volume":"248","author":"Gu","year":"2023","journal-title":"Exp. Biol. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40580-024-00414-9","article-title":"Polymeric DNase-I nanozymes targeting neutrophil extracellular traps for the treatment of bowel inflammation","volume":"11","author":"Wang","year":"2024","journal-title":"Nano Converg."},{"key":"ref_102","first-page":"e162","article-title":"Molecular mechanisms and therapeutic target of NETosis in diseases","volume":"3","author":"Huang","year":"2022","journal-title":"Med. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"eaav2309","DOI":"10.1126\/sciadv.aav2309","article-title":"Novel reprogramming of neutrophils modulates inflammation resolution during atherosclerosis","volume":"5","author":"Geng","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s41419-022-04809-6","article-title":"Generation of resolving memory neutrophils through pharmacological training with 4-PBA or genetic deletion of TRAM","volume":"13","author":"Lin","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1049\/nbt2.12137","article-title":"Neutrophil membrane biomimetic delivery system (Ptdser-NM-Lipo\/Fer-1) designed for targeting atherosclerosis therapy","volume":"17","author":"Li","year":"2023","journal-title":"IET Nanobiotechnology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7721","DOI":"10.1021\/acsnano.3c00288","article-title":"Neutrophil-membrane-coated biomineralized metal-organic framework nanoparticles for atherosclerosis treatment by targeting gene silencing","volume":"17","author":"Liu","year":"2023","journal-title":"ACS Nano"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jconrel.2019.02.034","article-title":"Ulcerative colitis-specific delivery of keratinocyte growth factor by neutrophils-simulated liposomes facilitates the morphologic and functional recovery of the damaged colon through alleviating the inflammation","volume":"299","author":"Zhao","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3899\/jrheum.2023-0833","article-title":"The link between dysregulated immunometabolism and vascular damage: Implications for the development of atherosclerosis in systemic lupus erythematosus and other rheumatic diseases","volume":"51","author":"Yennemadi","year":"2024","journal-title":"J. Rheumatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"E430","DOI":"10.1503\/cmaj.170776","article-title":"Managing premature atherosclerosis in patients with chronic inflammatory diseases","volume":"190","author":"Legge","year":"2018","journal-title":"Can. Med. Assoc. J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41584-023-01007-2","article-title":"Inflammation across tissues: Can shared cell biology help design smarter trials?","volume":"19","author":"Hosack","year":"2023","journal-title":"Nat. Rev. Rheumatol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/738\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:34:46Z","timestamp":1760031286000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,18]]},"references-count":110,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["cells14100738"],"URL":"https:\/\/doi.org\/10.3390\/cells14100738","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,18]]}}}