{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T22:04:16Z","timestamp":1794434656616,"version":"4.9.1"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"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>Amphiregulin (AREG), a member of the EGF family, exists as a transmembrane protein anchored to the cell surface. In response to external stimuli, its extracellular domain is released into the extracellular matrix through paracrine or autocrine signaling. However, its role in septic macrophage pyroptosis remains poorly understood. This study aims to investigate the role of extracellular AREG in septic macrophages, mice, and patients. We found that high expression of extracellular AREG was regulated by RPLP1 at the translation level, which increased the expression of IL-6, CCL2, and CCL3 protein, as well as <jats:italic>Caspase 1, IL-1\u03b2<\/jats:italic>, and <jats:italic>Nlrp3<\/jats:italic> mRNA expression, resulting in macrophage pyroptosis. Mechanistically, macrophage pyroptosis was aggravated by extracellular AREG pretreatment, which was triggered by extracellular AREG and ATP (adenosine 5\u2032-triphosphate). The AREG-neutralizing antibody reduced LPS-induced epidermal growth factor receptor (EGFR) activation, TLR4 expression, and pyroptosis. Extracellular AREG-induced macrophage pyroptosis decreased with EGFR and NF-\u03baB inhibition, as well as TLR4 and Myd88 knockout. Additionally, DTT-pretreated extracellular AREG suppressed macrophage pyroptosis. <jats:italic>In vivo<\/jats:italic>, extracellular AREG attenuates systemic inflammation infiltration and delays survival in a septic mouse model. Furthermore, extracellular AREG mediates sepsis in humans, and genes involved in the AREG-mediated pyroptosis signaling pathway were highly expressed in patients with severe sepsis compared with those with general or moderate sepsis. Overall, LPS-induced extracellular AREG aggravated or triggered macrophage pyroptosis through the EGFR\/TLR4\/Myd88\/NF-\u03baB signaling pathway, providing promising treatment strategies for sepsis.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1549749","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:15:05Z","timestamp":1744348505000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["LPS-induced extracellular AREG triggers macrophage pyroptosis through the EGFR\/TLR4 signaling pathway"],"prefix":"10.3389","volume":"16","author":[{"given":"Gang","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qudi","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aolin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihua","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(23)00330-2","article-title":"Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine","volume":"12","author":"Cajander","year":"2024","journal-title":"Lancet Respir Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.10.012","article-title":"The immunology of sepsis","volume":"54","author":"van der Poll","year":"2021","journal-title":"Immunity"},{"key":"B3","doi-asserted-by":"publisher","first-page":"6008","DOI":"10.3390\/ijms20236008","article-title":"Cytokines in inflammatory disease","volume":"20","author":"Kany","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41392-021-00687-0","article-title":"Pattern recognition receptors in health and diseases","volume":"6","author":"Li","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B5","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/s41573-021-00154-z","article-title":"Channelling inflammation: gasdermins in physiology and disease","volume":"20","author":"Liu","year":"2021","journal-title":"Nat Rev Drug Discovery"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2165918","DOI":"10.1155\/2019\/2165918","article-title":"Inhibition of synovial macrophage pyroptosis alleviates synovitis and fibrosis in knee osteoarthritis","volume":"2019","author":"Zhang","year":"2019","journal-title":"Mediators Inflammation"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.60292","article-title":"Cisplatin induces pyroptosis via activation of meg3\/nlrp3\/caspase-1\/gsdmd pathway in triple-negative breast cancer","volume":"17","author":"Yan","year":"2021","journal-title":"Int J Biol Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-017-0478-2","article-title":"Exocrine gland morphogenesis: insights into the role of amphiregulin from development to disease","volume":"65","author":"Sisto","year":"2017","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add7399","article-title":"Amphiregulin couples il1rl1(+) regulatory t cells and cancer-associated fibroblasts to impede antitumor immunity","volume":"9","author":"Sun","year":"2023","journal-title":"Sci Adv"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.v37.1","article-title":"Quercetin inhibits the amphiregulin\/egfr signaling-mediated renal tubular epithelial-mesenchymal transition and renal fibrosis in obstructive nephropathy","volume":"37","author":"Wang","year":"2023","journal-title":"Phytother Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.01.020","article-title":"Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair","volume":"42","author":"Zaiss","year":"2015","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1126\/science.1133715","article-title":"Amphiregulin, a th2 cytokine enhancing resistance to nematodes","volume":"314","author":"Zaiss","year":"2006","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn121430-20220822-00767","article-title":"Effect and mechanism of amphiregulin on acute respiratory distress syndrome in mice","volume":"35","author":"Li","year":"2023","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000001026","article-title":"Classically activated macrophages protect against lipopolysaccharide-induced acute lung injury by expressing amphiregulin in mice","volume":"124","author":"Xu","year":"2016","journal-title":"Anesthesiology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1038\/s41419-022-05370-y","article-title":"Egfr tyrosine kinase activity and rab gtpases coordinate egfr trafficking to regulate macrophage activation in sepsis","volume":"13","author":"Zhang","year":"2022","journal-title":"Cell Death Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1511794112","article-title":"Erlotinib protects against lps-induced endotoxicity because tlr4 needs egfr to signal","volume":"112","author":"De","year":"2015","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B17","doi-asserted-by":"publisher","first-page":"120863","DOI":"10.1016\/j.lfs.2022.120863","article-title":"Microrna-122a aggravates intestinal ischemia\/reperfusion injury by promoting pyroptosis via targeting egfr-nlrp3 signaling pathway","volume":"307","author":"Wang","year":"2022","journal-title":"Life Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/s41467-020-20577-3","article-title":"Targeting adaptor protein slp76 of rage as a therapeutic approach for lethal sepsis","volume":"12","author":"Yan","year":"2021","journal-title":"Nat Commun"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.v4.5","article-title":"Lilar, a novel long noncoding rna regulating autophagy in the liver tissues of endotoxemic mice through a competing endogenous rna mechanism","volume":"4","author":"Tian","year":"2023","journal-title":"MedComm (2020)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.11.005","article-title":"The multiomics landscape of serum exosomes during the development of sepsis","volume":"39","author":"Li","year":"2022","journal-title":"J Adv Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1146\/annurev-biophys-051013-022653","article-title":"Fidelity of cotranslational protein targeting by the signal recognition particle","volume":"43","author":"Zhang","year":"2014","journal-title":"Annu Rev Biophys"},{"key":"B22","doi-asserted-by":"publisher","first-page":"103086","DOI":"10.1016\/j.isci.2021.103086","article-title":"Ddx3 modulates the tumor microenvironment via its role in endoplasmic reticulum-associated translation","volume":"24","author":"Chen","year":"2021","journal-title":"iScience"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.09.039","article-title":"P-stalk ribosomes act as master regulators of cytokine-mediated processes","volume":"187","author":"Dopler","year":"2024","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7555\/JBR.31.20160039","article-title":"Ginkgol c17:1 inhibits tumor growth by blunting the egf- pi3k\/akt signaling pathway","volume":"31","author":"Li","year":"2017","journal-title":"J BioMed Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2014.12.010","article-title":"Modulation of the tumor microenvironment and inhibition of egf\/egfr pathway: novel anti-tumor mechanisms of cannabidiol in breast cancer","volume":"9","author":"Elbaz","year":"2015","journal-title":"Mol Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01125-1","article-title":"Tissue-resident macrophages exacerbate lung injury after remote sterile damage","volume":"21","author":"Zhong","year":"2024","journal-title":"Cell Mol Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","article-title":"The nuclear factor nf-kappab pathway in inflammation","volume":"1","author":"Lawrence","year":"2009","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s12974-022-02557-0","article-title":"Transforming growth factor-beta1 protects against lpc-induced cognitive deficit by attenuating pyroptosis of microglia via nf-kappab\/erk1\/2 pathways","volume":"19","author":"Xie","year":"2022","journal-title":"J Neuroinflamm"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2427094","DOI":"10.1080\/08916934.2024.2427094","article-title":"Mechanism of resveratrol on lps\/atp-induced pyroptosis and inflammatory response in ht29 cells","volume":"57","author":"Zhao","year":"2024","journal-title":"Autoimmunity"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93537","article-title":"Inflammasomes and il-1 biology in the pathogenesis of allograft dysfunction","volume":"127","author":"Weigt","year":"2017","journal-title":"J Clin Invest"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nature18629","article-title":"Inflammasome-activated gasdermin d causes pyroptosis by forming membrane pores","volume":"535","author":"Liu","year":"2016","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00740-6","article-title":"Nlrp3 inflammasome activation and cell death","volume":"18","author":"Huang","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1038\/s41598-017-01600-y","article-title":"Lipopolysaccharide-induced nf-kappab nuclear translocation is primarily dependent on myd88, but tnfalpha expression requires trif and myd88","volume":"7","author":"Sakai","year":"2017","journal-title":"Sci Rep"},{"key":"B34","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1111\/j.1474-9726.2010.00575.x","article-title":"Novel egf pathway regulators modulate c. Elegans healthspan and lifespan via egf receptor, plc-gamma, and ip3r activation","volume":"9","author":"Iwasa","year":"2010","journal-title":"Aging Cell"},{"key":"B35","doi-asserted-by":"publisher","first-page":"154484","DOI":"10.1016\/j.phymed.2022.154484","article-title":"Koumine regulates macrophage m1\/m2 polarization via tspo, alleviating sepsis-associated liver injury in mice","volume":"107","author":"Jin","year":"2022","journal-title":"Phytomedicine"},{"key":"B36","doi-asserted-by":"publisher","first-page":"108664","DOI":"10.1016\/j.biopha.2019.108664","article-title":"Mir-16 inhibits nlrp3 inflammasome activation by directly targeting tlr4 in acute lung injury","volume":"112","author":"Yang","year":"2019","journal-title":"BioMed Pharmacother"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.2001913","article-title":"Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction","volume":"12","author":"Xiao","year":"2021","journal-title":"Bioengineered"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0302628","article-title":"Mexenone protects mice from lps-induced sepsis by ec barrier stabilization","volume":"19","author":"Choi","year":"2024","journal-title":"PloS One"},{"key":"B39","doi-asserted-by":"publisher","first-page":"8232734","DOI":"10.1155\/2020\/8232734","article-title":"Meg3 alleviated lps-induced intestinal injury in sepsis by modulating mir-129-5p and surfactant protein d","volume":"2020","author":"Du","year":"2020","journal-title":"Mediators Inflammation"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1151728","article-title":"Circulating sepsis-related metabolite sphinganine could protect against intestinal damage during sepsis","volume":"14","author":"Wang","year":"2023","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"110678","DOI":"10.1016\/j.intimp.2023.110678","article-title":"Limonin, a novel ampk activator, protects against lps-induced acute lung injury","volume":"122","author":"Liang","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01368-w","article-title":"Liensinine reduces acute lung injury brought on by lipopolysaccharide by inhibiting the activation of the nf-kappab signaling pathway through modification of the src\/traf6\/tak1 axis","volume":"32","author":"Chen","year":"2024","journal-title":"Inflammopharmacology"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.2174\/1568026620666200303123102","article-title":"Review on epidermal growth factor receptor (egfr) structure, signaling pathways, interactions, and recent updates of egfr inhibitors","volume":"20","author":"Sabbah","year":"2020","journal-title":"Curr Top Med Chem"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e23488","DOI":"10.1096\/fj.202302385R","article-title":"Amphiregulin improves ventricular remodeling after myocardial infarction by modulating autophagy and apoptosis","volume":"38","author":"Li","year":"2024","journal-title":"FASEB J"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2015.10.061","article-title":"Membrane-tethered intracellular domain of amphiregulin promotes keratinocyte proliferation","volume":"136","author":"Stoll","year":"2016","journal-title":"J Invest Dermatol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2012.07.078","article-title":"Clarification of the c-terminal proteolytic processing site of human amphiregulin","volume":"586","author":"Levano","year":"2012","journal-title":"FEBS Lett"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.09.037","article-title":"Amphiregulin may be a new biomarker of classically activated macrophages","volume":"466","author":"Meng","year":"2015","journal-title":"Biochem Biophys Res Commun"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.yexcr.2018.08.009","article-title":"Epidermal growth factor receptor: structure-function informing the design of anticancer therapeutics","volume":"371","author":"Mitchell","year":"2018","journal-title":"Exp Cell Res"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209942","article-title":"Nuclear factor-kappab and inhibitor of kappab kinase pathways in oncogenic initiation and progression","volume":"25","author":"Basseres","year":"2006","journal-title":"Oncogene"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209954","article-title":"Introduction to nf-kappab: players, pathways, perspectives","volume":"25","author":"Gilmore","year":"2006","journal-title":"Oncogene"},{"key":"B51","doi-asserted-by":"publisher","first-page":"5407","DOI":"10.1038\/onc.2015.313","article-title":"Epidermal growth factor (egf) activates nuclear factor-kappab through ikappabalpha kinase-independent but egf receptor-kinase dependent tyrosine 42 phosphorylation of ikappabalpha","volume":"34","author":"Sethi","year":"2015","journal-title":"Oncogene"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2022.2067676","article-title":"Beta-carotene regulates the biological activity of egf in iec6 cells by alleviating the inflammatory process","volume":"21","author":"Guoxia","year":"2022","journal-title":"Cell Cycle"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.2014.18.issue-2","article-title":"The role of egf-egfr signalling pathway in hepatocellular carcinoma inflammatory microenvironment","volume":"18","author":"Huang","year":"2014","journal-title":"J Cell Mol Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-019-00668-8","article-title":"Egfr signaling augments tlr4 cell surface expression and function in macrophages via regulation of rab5a activation","volume":"11","author":"Tang","year":"2020","journal-title":"Protein Cell"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606781200","article-title":"Role of tlr4 tyrosine phosphorylation in signal transduction and endotoxin tolerance","volume":"282","author":"Medvedev","year":"2007","journal-title":"J Biol Chem"},{"key":"B56","doi-asserted-by":"publisher","first-page":"8739473","DOI":"10.1155\/2018\/8739473","article-title":"Role of epidermal growth factor receptor (egfr) and its ligands in kidney inflammation and damage","volume":"2018","author":"Rayego-Mateos","year":"2018","journal-title":"Mediators Inflammation"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.08.010","article-title":"Regulatory t cells require il6 receptor alpha signaling to control skeletal muscle function and regeneration","volume":"35","author":"Becker","year":"2023","journal-title":"Cell Metab"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514","article-title":"Cleavage of gsdmd by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2003-0281RC","article-title":"Fine particulate matter induces amphiregulin secretion by bronchial epithelial cells","volume":"30","author":"Blanchet","year":"2004","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.12.023","article-title":"Metalloprotease-dependent amphiregulin release mediates tumor necrosis factor-alpha-induced il-8 secretion in the human airway epithelial cell line nci-h292","volume":"78","author":"Chokki","year":"2006","journal-title":"Life Sci"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606532200","article-title":"Autocrine and juxtacrine effects of amphiregulin on the proliferative, invasive, and migratory properties of normal and neoplastic human mammary epithelial cells","volume":"281","author":"Willmarth","year":"2006","journal-title":"J Biol Chem"},{"key":"B62","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1007\/s00018-023-04709-8","article-title":"The role of amphiregulin in ovarian function and disease","volume":"80","author":"Fang","year":"2023","journal-title":"Cell Mol Life Sci"},{"key":"B63","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13045-018-0689-y","article-title":"Multiple myeloma-derived exosomes are enriched of amphiregulin (areg) and activate the epidermal growth factor pathway in the bone microenvironment leading to osteoclastogenesis","volume":"12","author":"Raimondo","year":"2019","journal-title":"J Hematol Oncol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.canlet.2007.01.015","article-title":"Amphiregulin: a new growth factor in hepatocarcinogenesis","volume":"254","author":"Berasain","year":"2007","journal-title":"Cancer Lett"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2011.05.003","article-title":"The multiple roles of amphiregulin in human cancer","volume":"1816","author":"Busser","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"B66","article-title":"Areg mediates the epithelial\u2212mesenchymal transition in pancreatic cancer cells via the egfr\/erk\/nf\u2212kappab signalling pathway","volume":"43","author":"Wang","year":"2020","journal-title":"Oncol Rep"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2024.07.004","article-title":"Sustained amphiregulin expression in intermediate alveolar stem cells drives progressive fibrosis","volume":"31","author":"Zhao","year":"2024","journal-title":"Cell Stem Cell"},{"key":"B68","doi-asserted-by":"publisher","first-page":"104355","DOI":"10.1016\/j.ebiom.2022.104355","article-title":"How sepsis parallels and differs from covid-19","volume":"86","author":"Herminghaus","year":"2022","journal-title":"EBioMedicine"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.86424","article-title":"Adar1 protects pulmonary macrophages from sepsis-induced pyroptosis and lung injury through mir-21\/a20 signaling","volume":"20","author":"Zhao","year":"2024","journal-title":"Int J Biol Sci"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.720109","article-title":"Monocytes and macrophages in covid-19","volume":"12","author":"Knoll","year":"2021","journal-title":"Front Immunol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.eng.2021.05.009","article-title":"Identification of monocytes associated with severe covid-19 in the pbmcs of severely infected patients through single-cell transcriptome sequencing","volume":"17","author":"Zhang","year":"2022","journal-title":"Eng (Beijing)"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00681-2","article-title":"Single-cell rna sequencing of blood antigen-presenting cells in severe covid-19 reveals multi-process defects in antiviral immunity","volume":"23","author":"Saichi","year":"2021","journal-title":"Nat Cell Biol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1549749\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:15:07Z","timestamp":1744348507000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1549749\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":72,"alternative-id":["10.3389\/fimmu.2025.1549749"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1549749","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]},"article-number":"1549749"}}