{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:53:40Z","timestamp":1792072420406,"version":"4.4.0"},"reference-count":90,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"80","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,2,3]]},"abstract":"<jats:p>\n                    The complement component C3 is a fundamental plasma protein for host defense, produced largely by the liver. However, recent work has demonstrated the critical importance of tissue-specific C3 expression in cell survival. Here, we analyzed the effects of local versus peripheral sources of C3 expression in a model of acute bacterial pneumonia induced by\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    . Whereas mice with global C3 deficiency had severe pneumonia-induced lung injury, those deficient only in liver-derived C3 remained protected, comparable to wild-type mice. Human lung transcriptome analysis showed that secretory epithelial cells, such as club cells, express high levels of C3 mRNA. Mice with tamoxifen-induced C3 gene ablation from club cells in the lung had worse pulmonary injury compared with similarly treated controls, despite maintaining normal circulating C3 levels. Last, in both the mouse pneumonia model and cultured primary human airway epithelial cells, we showed that stress-induced death associated with C3 deficiency parallels that seen in Factor B deficiency rather than C3a receptor deficiency. Moreover, C3-mediated reduction in epithelial cell death requires alternative pathway component Factor B.\u00a0Thus, our findings suggest that a pathway reliant on locally derived C3 and Factor B protects the lung mucosal barrier.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.abp9547","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T13:58:23Z","timestamp":1675432703000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":73,"title":["Lung epithelial cell\u2013derived C3 protects against pneumonia-induced lung injury"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4638-5095","authenticated-orcid":true,"given":"Sanjaya K.","family":"Sahu","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0187-3642","authenticated-orcid":true,"given":"Ay\u015fe N.","family":"Ozant\u00fcrk","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-8205","authenticated-orcid":true,"given":"Devesha H.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0970-0893","authenticated-orcid":true,"given":"Lina","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1171-9761","authenticated-orcid":true,"given":"Ruteja A.","family":"Barve","sequence":"additional","affiliation":[{"name":"Department of Genetics, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linus","family":"Dannull","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4227-7852","authenticated-orcid":true,"given":"Marick","family":"Starick","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ja\u2019Nia","family":"McPhatter","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Garnica","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4298-5544","authenticated-orcid":true,"given":"Maxwell","family":"Sanfillipo-Burchman","sequence":"additional","affiliation":[{"name":"Division of Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Kunen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-6343","authenticated-orcid":true,"given":"Andrew E.","family":"Gelman","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0905-7527","authenticated-orcid":true,"given":"Steven L.","family":"Brody","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2514-3441","authenticated-orcid":true,"given":"John P.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4830-5084","authenticated-orcid":true,"given":"Hrishikesh S.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, John T.\u00a0Milliken Department of Medicine, Washington University School of Medicine, St.\u00a0Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00032.2017"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00259-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1608077"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0069-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.202102-209ST"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2021.09.002"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201910-2083OC"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012669199"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.2899-2906.2004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.08.017"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00520-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256070"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.04.008"},{"key":"e_1_3_3_15_2","first-page":"21","article-title":"Serum complement after orthotopic transplantation of the human liver","volume":"12","author":"Torisu M.","year":"1972","unstructured":"M.\u00a0Torisu, T.\u00a0Yokoyama, P. F.\u00a0Kohler, A. L.\u00a0Durst, G.\u00a0Martineau, G.\u00a0Schroter, H.\u00a0Amemiya, C. G.\u00a0Groth, T. E.\u00a0Starzl, Serum complement after orthotopic transplantation of the human liver. Clin. Exp. Immunol. 12, 21\u201330 (1972).","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05172"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41312-z"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.02.006"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2017-0405OC"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.09.009"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.03.003"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abg0833"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-022-00534-7"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.11.046"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89412"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00127.2006"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-089821"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/mab.2014.0066"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701668"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2015-207035"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2016-209598"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020-0308LE"},{"key":"e_1_3_3_33_2","first-page":"112","article-title":"A census of the lung: CellCards from LungMAP","author":"Sun X.","year":"2021","unstructured":"X.\u00a0Sun, A.-K.\u00a0Perl, R.\u00a0Li, S. M.\u00a0Bell, E.\u00a0Sajti, V. V.\u00a0Kalinichenko, T. V.\u00a0Kalin, R. S.\u00a0Misra, H.\u00a0Deshmukh, G.\u00a0Clair, J.\u00a0Kyle, L. E.\u00a0Crotty Alexander, J. M.\u00a0Silva, J. A.\u00a0Kitzmiller, K. A.\u00a0Wikenheiser-Brokamp, G.\u00a0Deutsch, M.\u00a0Guo, Y.\u00a0Du, M. P.\u00a0Morley, M. J.\u00a0Valdez, H. V.\u00a0Yu, K.\u00a0Jin, E. E.\u00a0Bardes, J. A.\u00a0Zepp, T.\u00a0Neithamer, M. C.\u00a0Basil, W. J.\u00a0Zacharias, J.\u00a0Verheyden, R.\u00a0Young, G.\u00a0Bandyopadhyay, S.\u00a0Lin, C.\u00a0Ansong, J.\u00a0Adkins, N.\u00a0Salomonis, B. J.\u00a0Aronow, Y.\u00a0Xu, G.\u00a0Pryhuber, J.\u00a0Whitsett, E. E.\u00a0Morrisey; NHLBI LungMAP consortium, A census of the lung: CellCards from LungMAP. Dev. Cell , 112\u2013145.e2 (2021).","journal-title":"Dev. Cell"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.14.6.8652187"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.17.3.2774"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204710109"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2020-207242"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1814"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00155107"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1210"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.08.003"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0210-0"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-021-00873-w"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.08.003"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.05.019"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12474"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.40.4.544"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0188OC"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0256RC"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.04.002"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.018"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.4.545"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.009"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf2489"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.628062"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2655-1"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.03.038"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02373-2021"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021-0463OC"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-014-9633-4"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2017.03.72"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26460-z"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.148382"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01675"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abh2259"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00395.2017"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173257"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8720"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2004.06.048"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2020.108598"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP280389"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-3109(99)00021-1"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.10.5406"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301903"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12997"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119828"},{"key":"e_1_3_3_77_2","unstructured":"Details about the COMPBIO biological knowledge generation platform are available on the websites of the Washington University School Medical Library (https:\/\/becker.wustl.edu\/resources\/software\/compbio\/) and the company website for PercayAI (www.percayai.com\/tech)."},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021-0531ST"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.24"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13326-019-0209-1"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201911-2199OC"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16239-z"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201712-2410OC"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1983"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1972"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500352"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98436"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.039172"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603310113"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00077-15"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M076141"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.abp9547","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T07:43:17Z","timestamp":1705390997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.abp9547"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,3]]},"references-count":90,"journal-issue":{"issue":"80","published-print":{"date-parts":[[2023,2,3]]}},"alternative-id":["10.1126\/sciimmunol.abp9547"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.abp9547","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.02.03.478963","asserted-by":"object"}]},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,3]]},"assertion":[{"value":"2022-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eabp9547"}}