{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T13:29:03Z","timestamp":1793366943071,"version":"4.5.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"22","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,5,31]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Resolution of inflammation is an active process that restores tissue homeostasis and prevents the development of chronic inflammatory diseases. The mechanisms that regulate resolution of inflammation are only partially understood. Here, we showed that activation of the vagus nerve accelerated resolution of inflammation. Electrical stimulation of the vagus nerve in\u00a0vivo increased levels of select specialized proresolving mediators in inflammation. Experiments in genetic mouse models revealed that the mechanism involved 12\/15-lipoxgenase (Alox15), a key enzyme for biosynthesis of the identified mediators, and required the \u03b17-nicotinic acetylcholine receptor subunit. The findings indicate that electrical signals in the vagus nerve activate a cholinergic signal promoting Alox15-dependent lipid mediator biosynthesis and accelerating resolution of inflammation, providing additional insights into neural regulation of inflammation.<\/jats:p>","DOI":"10.1073\/pnas.2023285119","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T13:51:13Z","timestamp":1653659473000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":85,"title":["Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the \u03b17nAChR subunit"],"prefix":"10.1073","volume":"119","author":[{"given":"April S.","family":"Caravaca","sequence":"first","affiliation":[{"name":"Laboratory of Immunobiology, Division of Cardiovascular Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, 171 76, Sweden"},{"name":"Stockholm Center for Bioelectronic Medicine, MedTechLabs, Karolinska University Hospital, Solna, 171 76, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-8309","authenticated-orcid":false,"given":"Alessandro L.","family":"Gallina","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Division of Cardiovascular Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, 171 76, Sweden"},{"name":"Stockholm Center for Bioelectronic Medicine, MedTechLabs, Karolinska University Hospital, Solna, 171 76, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Tarnawski","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Division of Cardiovascular Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, 171 76, Sweden"},{"name":"Stockholm Center for Bioelectronic Medicine, MedTechLabs, Karolinska University Hospital, Solna, 171 76, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir S.","family":"Shavva","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Division of Cardiovascular Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, 171 76, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain A.","family":"Colas","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6328-3640","authenticated-orcid":false,"given":"Jesmond","family":"Dalli","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-9579","authenticated-orcid":false,"given":"Stephen G.","family":"Malin","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Division of Cardiovascular Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, 171 76, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9210-121X","authenticated-orcid":false,"given":"Henrik","family":"Hult","sequence":"additional","affiliation":[{"name":"Stockholm Center for Bioelectronic Medicine, MedTechLabs, Karolinska University Hospital, Solna, 171 76, Sweden"},{"name":"Department of Mathematics, KTH Royal Institute of Technology, Stockholm, 114 28, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5163-3946","authenticated-orcid":false,"given":"Hildur","family":"Arnardottir","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Division of Cardiovascular Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, 171 76, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3473-5948","authenticated-orcid":false,"given":"Peder S.","family":"Olofsson","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Division of Cardiovascular Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, 171 76, Sweden"},{"name":"Stockholm Center for Bioelectronic Medicine, MedTechLabs, Karolinska University Hospital, Solna, 171 76, Sweden"},{"name":"Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, New York, 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13479"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12859"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2015.03.004"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05800-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00160"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.39"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01138.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053158"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/35013070"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.15424\/bioelectronmed.2015.00006"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02648"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00877"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01339"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209985"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00405"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1605635113"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a034181"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00837.2004"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/430323"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.02.022"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4477"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20132103"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800806"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","unstructured":"R. A. Colas E. A. Gomez J. Dalli Methodologies and procedures employed in the identification and quantitation of lipid mediators via LC-MS\/MS. ResearchGate [Preprint] (2020). https:\/\/www.researchgate.net\/publication\/346484981_Methodologies_and_Procedures_Employed_in_the_Identification_and_Quantitation_of_Lipid_Mediators_via_LC-MSMS (Accessed 13 January 2022).","DOI":"10.21203\/rs.3.pex-1147\/v1"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19176-z"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.573019"},{"key":"e_1_3_4_27_2","first-page":"737","article-title":"Steps toward minimal reporting standards for lipidomics mass spectrometry in biomedical research publications","volume":"13","author":"Odonnell V. B.","year":"2020","unstructured":"V. B. Odonnell , Steps toward minimal reporting standards for lipidomics mass spectrometry in biomedical research publications. Circ. Genom. Precis. Med. 13, 737\u2013741 (2020).","journal-title":"Circ. Genom. Precis. Med."},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.7.4345"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.12.009"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.99"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401313"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.1663"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7592-1_4"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2041"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemolab.2004.12.011"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"a016311","DOI":"10.1101\/cshperspect.a016311","article-title":"Lipid mediators in the resolution of inflammation","volume":"7","author":"Serhan C. N.","year":"2014","unstructured":"C. N. Serhan, N. Chiang, J. Dalli, B. D. Levy, Lipid mediators in the resolution of inflammation. Cold Spring Harb. Perspect. Biol. 7, a016311 (2014).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2014.08.006"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11042"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05877"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102362"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150225"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1395-17.2017"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1177\/2047487317694464"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2017.08.007"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-019-00767-y"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1365-2796.2010.02226.x","article-title":"Whole blood cytokine attenuation by cholinergic agonists ex vivo and relationship to vagus nerve activity in rheumatoid arthritis","volume":"268","author":"Bruchfeld A.","year":"2010","unstructured":"A. Bruchfeld , Whole blood cytokine attenuation by cholinergic agonists ex vivo and relationship to vagus nerve activity in rheumatoid arthritis. J. Intern. Med. 268, 94\u2013101 (2010).","journal-title":"J. Intern. Med."},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2014.03.006"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13202"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101736"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1470922"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-002-0254-9"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410638200"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc11518"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303892"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2023285119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T04:07:45Z","timestamp":1700626065000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2023285119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,27]]},"references-count":54,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2022,5,31]]}},"alternative-id":["10.1073\/pnas.2023285119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2023285119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,27]]},"assertion":[{"value":"2020-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2023285119"}}