{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:32Z","timestamp":1787034332736,"version":"build-2736575974"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pathological NETosis contributes to immune dysregulation and organ damage in systemic lupus erythematosus (SLE), positioning it as a potential therapeutic target. Previous studies have shown suppressed NETosis in term low birth weight (tLBW) newborns. Several NETosis-suppressive molecules, including the \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      -antitrypsin-derived C-terminal peptide and CRISPP have been reported in cord blood (CB) plasma and have shown suppressive effects on NET formation. Given the pathogenic role of excessive NETosis in SLE, these observations suggest that LBW newborns\u2019 CB plasma (LP) may contain putative NETosis-inhibitory factors with therapeutic potential and support further investigations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the NETosis-inhibitory activity of LP and its effects on lupus-associated pathological features in neutrophils from patients with SLE and in the pristane-induced lupus (PIL) mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Ex vivo<\/jats:italic>\n                      effects of LP on NETosis were evaluated using neutrophils from patients with SLE (n=35) and PIL mouse (n=18; n=6\/group). NET formation was assessed by extracellular DNA release and expression of key markers, including citrullinated histone H3 (CitH3), neutrophil elastase (NE), and myeloperoxidase (MPO), along with cytoplasmic and mitochondrial ROS production.\n                      <jats:italic>In vivo<\/jats:italic>\n                      efficacy was determined by measuring reduction in NETosis, oxidative stress, anti-dsDNA autoantibody levels, proteinuria, and improvement of tissue oxygenation and vascularization in the heart, liver and kidneys of PIL mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LP significantly reduced NET formation, as evidenced by reduced extracellular DNA release and expression of CitH3 and NE in SLE neutrophils. Extracellular DNA release decreased by 13% and 16.66% along with a reduction in netting neutrophils by 27.4% and 21.12% under basal and LPS-stimulated conditions, respectively. LP also suppressed ROS production in SLE neutrophils. In PIL mice, LP reduced NETosis (30.93%) and oxidative stress (15.34%mitochondrial ROS; 24.28% cytoplasmic ROS) in blood-derived neutrophils, decreased MPO and Sytox Orange signal intensities in the heart, liver, and kidneys. LP further decreased anti-dsDNA autoantibody levels (57.9%) and proteinuria (93.59%), preserved vascular integrity, and improved tissue oxygenation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      LP exhibits NETosis-inhibitory activity and ameliorates lupus-associated pathology in the PIL mouse and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      SLE neutrophil system. These findings suggest the presence of as-yet-uncharacterized endogenous plasma components that modulate NET formation and support further investigation as potential therapeutics for SLE.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1863546","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:38:10Z","timestamp":1787031490000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["NETosis inhibitory activity of LBW newborns\u2019 cord blood plasma reverses lupus-associated immunopathology"],"prefix":"10.3389","volume":"17","author":[{"given":"Hiral","family":"Thacker","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University","place":["Varanasi, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushbu","family":"Priya","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Molecular Immunology Section, National Eye Institute, National Institutes of Health","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Medical Sciences, Banaras Hindu University","place":["Varanasi, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shambhavi","family":"Singh","sequence":"additional","affiliation":[{"name":"School of Medicine, D Y Patil University","place":["Navi Mumbai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manaswi","family":"Chaubey","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University","place":["Varanasi, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geeta","family":"Rai","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University","place":["Varanasi, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02168-0","article-title":"Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics","volume":"10","author":"Dai","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3390\/pathophysiology32040061","article-title":"Immunopathogenesis of systemic lupus erythematosus: interplay of innate and adaptive immunity, microbiome dysbiosis, and emerging therapeutic targets","volume":"32","author":"Ahmed","year":"2025","journal-title":"Pathophysiology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"9493","DOI":"10.3390\/ijms24119493","article-title":"Galectin-3 mediates NETosis and acts as an autoantigen in systemic lupus erythematosus-associated diffuse alveolar haemorrhage","volume":"24","author":"Chen","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201719","article-title":"Neutrophil extracellular traps: double-edged swords of innate immunity","volume":"189","author":"Kaplan","year":"2012","journal-title":"J Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-013-0384-6","article-title":"Molecular mechanisms regulating NETosis in infection and disease","volume":"35","author":"Branzk","year":"2013","journal-title":"Semin Immunopathol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"35","DOI":"10.14740\/jocmr6129","article-title":"Organ damage and its associated factors in systemic lupus erythematosus patients: a retrospective cohort study","volume":"17","author":"Alharbi","year":"2025","journal-title":"J Clin Med Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/art.42863","article-title":"Unique interplay between antinuclear antibodies and nuclear molecules in the pathogenesis of systemic lupus erythematosus","volume":"76","author":"Pisetsky","year":"2024","journal-title":"Arthritis Rheumatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00787-0","article-title":"Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases","volume":"23","author":"Wigerblad","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"7989","DOI":"10.2147\/JIR.S526936","article-title":"Neutrophil extracellular traps (NETs) in sterile inflammatory diseases","volume":"18","author":"Ji","year":"2025","journal-title":"J Inflammation Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/s43556-025-00337-9","article-title":"Neutrophil extracellular traps (NETs) in health and disease","volume":"6","author":"Shahzad","year":"2025","journal-title":"Mol BioMed"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2014.942288","article-title":"Immune responses in neonates","volume":"10","author":"Basha","year":"2014","journal-title":"Expert Rev Clin Immunol"},{"key":"B12","unstructured":"Global Nutrition Targets 2025: Low Birth Weight Policy Brief\n          \n          2014"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/08880018.2023.2218409","article-title":"Innate immune mechanism of neutrophil extracellular trap formation is impaired in at-risk term low birth weight newborns","volume":"40","author":"Das","year":"2023","journal-title":"Pediatr Hematol Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000000416","article-title":"Decreased toll-like receptor 4\/myeloid differentiation factor 88 response leads to defective interleukin 1\u03b2 production in term low birth weight newborns","volume":"33","author":"Singh","year":"2014","journal-title":"Pediatr Infect Dis J"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e62845","DOI":"10.1371\/journal.pone.0062845","article-title":"Decreased pattern recognition receptor signaling, interferon signature, and bactericidal\/permeability-increasing protein gene expression in cord blood of term low birth weight human newborns","volume":"8","author":"Singh","year":"2013","journal-title":"PloS One"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113165","article-title":"Complement component 5a receptor 1 and leukotriene B4 receptor 1 regulate neutrophil extracellular trap (NET) formation through Rap1a\/B-Raf\/ERK signaling pathway and their deficiency in term low birth weight newborns leads to deficient NETosis","volume":"142","author":"Das","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83873","article-title":"Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation","volume":"126","author":"Yost","year":"2016","journal-title":"J Clin Invest"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/antiox15010025","article-title":"Neutrophil extracellular traps in systemic lupus erythematosus: pathogenic mechanisms, crosstalk with oxidative stress, and antioxidant therapeutic potential","volume":"15","author":"Chen","year":"2025","journal-title":"Antioxidants (Basel)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241713581","article-title":"The role of neutrophil extracellular traps (NETs) in the pathogenesis of systemic lupus erythematosus and antiphospholipid syndrome","volume":"24","author":"Reshetnyak","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1461841","article-title":"Dexamethasone and IFN-\u03b3 primed mesenchymal stem cells conditioned media immunomodulates aberrant NETosis in SLE via PGE2 and IDO","volume":"15","author":"Priya","year":"2024","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/s41419-020-2497-x","article-title":"In vivo evidence for extracellular DNA trap formation","volume":"11","author":"Yousefi","year":"2020","journal-title":"Cell Death Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1046574","article-title":"Neonatal NET-Inhibitory Factor improves survival in the cecal ligation and puncture model of polymicrobial sepsis by inhibiting neutrophil extracellular traps","volume":"13","author":"de Araujo","year":"2023","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1863546\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:38:11Z","timestamp":1787031491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1863546\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":22,"alternative-id":["10.3389\/fimmu.2026.1863546"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1863546","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"article-number":"1863546"}}