{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:34:13Z","timestamp":1792596853473,"version":"4.5.0"},"reference-count":81,"publisher":"Rockefeller University Press","issue":"5","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI160167"],"award-info":[{"award-number":["R01 AI160167"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI165919"],"award-info":[{"award-number":["AI165919"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 HL161241"],"award-info":[{"award-number":["R35 HL161241"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL143896"],"award-info":[{"award-number":["R01 HL143896"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL059157"],"award-info":[{"award-number":["HL059157"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL127402"],"award-info":[{"award-number":["HL127402"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008069","name":"University of California, San Francisco","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,5]]},"abstract":"<jats:p>Intravital microscopy has enabled the study of immune dynamics in the pulmonary microvasculature, but many key events remain unseen because they occur in deeper lung regions. We therefore developed a technique for stabilized intravital imaging of bronchovascular cuffs and collecting lymphatics surrounding pulmonary veins in mice. Intravital imaging of pulmonary lymphatics revealed ventilation dependence of steady-state lung lymph flow and ventilation-independent lymph flow during inflammation. We imaged the rapid exodus of migratory dendritic cells through lung lymphatics following inflammation and measured effects of pharmacologic and genetic interventions targeting chemokine signaling. Intravital imaging also captured lymphatic immune surveillance of lung-metastatic cancers and lymphatic metastasis of cancer cells. To our knowledge, this is the first imaging of lymph flow and leukocyte migration through intact pulmonary lymphatics. This approach will enable studies of protective and maladaptive processes unfolding within the lungs and in other previously inaccessible locations.<\/jats:p>","DOI":"10.1084\/jem.20241359","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T10:11:56Z","timestamp":1739959916000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer"],"prefix":"10.1084","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5573-6363","authenticated-orcid":true,"given":"Simon J.","family":"Cleary","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco (UCSF) 1 Department of Medicine, , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/0220mzb33","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pharmaceutical Science, King\u2019s College London 2 , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3122-9679","authenticated-orcid":true,"given":"Longhui","family":"Qiu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco (UCSF) 1 Department of Medicine, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1281-0919","authenticated-orcid":true,"given":"Yurim","family":"Seo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco (UCSF) 1 Department of Medicine, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2219-2616","authenticated-orcid":true,"given":"Peter","family":"Baluk","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Cardiovascular Research Institute, and Helen Diller Family Comprehensive Cancer Center, UCSF 3 Department of Anatomy, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5601-8053","authenticated-orcid":true,"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Howard Hughes Medical Institute, UCSF 4 Department of Microbiology and Immunology, , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/05hfa4n20","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Medicine, Westlake University 5 Westlake Laboratory of Life Sciences and Biomedicine, , Hangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2243-5446","authenticated-orcid":true,"given":"Nina K.","family":"Serwas","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"UCSF 6 Department of Pathology, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7664-5606","authenticated-orcid":true,"given":"Catherine A.","family":"Taylor","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco (UCSF) 1 Department of Medicine, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2500-1341","authenticated-orcid":true,"given":"Dongliang","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco (UCSF) 1 Department of Medicine, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-9745","authenticated-orcid":true,"given":"Jason G.","family":"Cyster","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Howard Hughes Medical Institute, UCSF 4 Department of Microbiology and Immunology, , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Bakar ImmunoX Initiative, UCSF 7 , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6985-9564","authenticated-orcid":true,"given":"Donald M.","family":"McDonald","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Cardiovascular Research Institute, and Helen Diller Family Comprehensive Cancer Center, UCSF 3 Department of Anatomy, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-3533","authenticated-orcid":true,"given":"Matthew F.","family":"Krummel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"UCSF 6 Department of Pathology, , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Bakar ImmunoX Initiative, UCSF 7 , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0241-9190","authenticated-orcid":true,"given":"Mark R.","family":"Looney","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco (UCSF) 1 Department of Medicine, , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Bakar ImmunoX Initiative, UCSF 7 , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"2025021915034511500_bib1","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1056\/NEJM200005043421801","article-title":"Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome","volume":"342","author":"Acute Respiratory Distress Syndrome Network","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"2025021915034511500_bib2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201413","article-title":"Upregulation of VCAM-1 in lymphatic collectors supports dendritic cell entry and rapid migration to lymph nodes in inflammation","volume":"218","author":"Arasa","year":"2021","journal-title":"J. Exp. Med."},{"key":"2025021915034511500_bib3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s10637-023-01410-2","article-title":"CXCR2 antagonist navarixin in combination with pembrolizumab in select advanced solid tumors: A phase 2 randomized trial","volume":"42","author":"Armstrong","year":"2024","journal-title":"Invest. New Drugs"},{"key":"2025021915034511500_bib4","doi-asserted-by":"publisher","DOI":"10.3791\/66566","article-title":"Intravital two-photon microscopy of the transplanted mouse lung","author":"Bai","year":"2024","journal-title":"J. Vis. Exp."},{"key":"2025021915034511500_bib5","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/978-1-4939-8712-2_11","article-title":"Imaging lymphatics in mouse lungs","volume":"1846","author":"Baluk","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"2025021915034511500_bib6","doi-asserted-by":"publisher","first-page":"a041178","DOI":"10.1101\/cshperspect.a041178","article-title":"Buttons and zippers: Endothelial junctions in lymphatic vessels","volume":"12","author":"Baluk","year":"2022","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"2025021915034511500_bib7","doi-asserted-by":"publisher","first-page":"2355","DOI":"10.1016\/j.ajpath.2020.08.018","article-title":"Lymphatic proliferation ameliorates pulmonary fibrosis after lung injury","volume":"190","author":"Baluk","year":"2020","journal-title":"Am. J. Pathol."},{"key":"2025021915034511500_bib8","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1038\/s41592-023-02004-9","article-title":"Crystal ribcage: A platform for probing real-time lung function at cellular resolution","volume":"20","author":"Banerji","year":"2023","journal-title":"Nat. Methods"},{"key":"2025021915034511500_bib9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1146\/annurev-immunol-061020-053707","article-title":"Dendritic cells revisited","volume":"39","author":"Cabeza-Cabrerizo","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"2025021915034511500_bib10","doi-asserted-by":"publisher","first-page":"4042","DOI":"10.1172\/JCI76509","article-title":"Intravital imaging of intestinal lacteals unveils lipid drainage through contractility","volume":"125","author":"Choe","year":"2015","journal-title":"J. Clin. Invest."},{"key":"2025021915034511500_bib11","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1182\/blood-2010-07-298562","article-title":"Visualization of lymphatic vessels by Prox1-promoter directed GFP reporter in a bacterial artificial chromosome-based transgenic mouse","volume":"117","author":"Choi","year":"2011","journal-title":"Blood"},{"key":"2025021915034511500_bib12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211830","article-title":"Infection-induced lymphatic zippering restricts fluid transport and viral dissemination from skin","volume":"219","author":"Churchill","year":"2022","journal-title":"J. Exp. Med."},{"key":"2025021915034511500_bib13","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1165\/rcmb.2018-0182OC","article-title":"LPS-induced lung platelet recruitment occurs independently from neutrophils, PSGL-1, and P-selectin","volume":"61","author":"Cleary","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2025021915034511500_bib14","doi-asserted-by":"publisher","first-page":"5909","DOI":"10.1172\/JCI138136","article-title":"Complement activation on endothelium initiates antibody-mediated acute lung injury","volume":"130","author":"Cleary","year":"2020","journal-title":"J. Clin. Invest."},{"key":"2025021915034511500_bib15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI178351","article-title":"IgG hexamers initiate complement-dependent acute lung injury","volume":"134","author":"Cleary","year":"2024","journal-title":"J. Clin. Invest."},{"key":"2025021915034511500_bib16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/imr.13030","article-title":"Imaging leukocyte migration through afferent lymphatics","volume":"306","author":"Collado-Diaz","year":"2022","journal-title":"Immunol. Rev."},{"key":"2025021915034511500_bib17","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.149870","article-title":"ADAM8 signaling drives neutrophil migration and ARDS severity","volume":"7","author":"Conrad","year":"2022","journal-title":"JCI Insight"},{"key":"2025021915034511500_bib18","doi-asserted-by":"publisher","first-page":"1917484","DOI":"10.1080\/19420862.2021.1917484","article-title":"Targeting cancer homing into the lymph node with a novel anti-CCR7 therapeutic antibody: The paradigm of CLL","volume":"13","author":"Cuesta-Mateos","year":"2021","journal-title":"MAbs"},{"key":"2025021915034511500_bib19","doi-asserted-by":"publisher","first-page":"2960","DOI":"10.4049\/jimmunol.175.5.2960","article-title":"Sphingosine-1-phosphate mediates migration of mature dendritic cells","volume":"175","author":"Czeloth","year":"2005","journal-title":"J. Immunol."},{"key":"2025021915034511500_bib20","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/j.it.2019.08.002","article-title":"Adventitial cuffs: Regional hubs for tissue immunity","volume":"40","author":"Dahlgren","year":"2019","journal-title":"Trends Immunol."},{"key":"2025021915034511500_bib21","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1080\/10739680600893909","article-title":"Lymph flow, shear stress, and lymphocyte velocity in rat mesenteric prenodal lymphatics","volume":"13","author":"Dixon","year":"2006","journal-title":"Microcirculation"},{"key":"2025021915034511500_bib22","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/nmeth.4511","article-title":"A permanent window for the murine lung enables high-resolution imaging of cancer metastasis","volume":"15","author":"Entenberg","year":"2018","journal-title":"Nat. Methods"},{"key":"2025021915034511500_bib23","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.celrep.2018.03.072","article-title":"Manifold roles of CCR7 and its ligands in the induction and maintenance of bronchus-associated lymphoid tissue","volume":"23","author":"Fleige","year":"2018","journal-title":"Cell Rep."},{"key":"2025021915034511500_bib24","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1165\/rcmb.2016-0261TR","article-title":"Cardiomyocytes of the heart and pulmonary veins: Novel contributors to asthma?","volume":"57","author":"Folmsbee","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2025021915034511500_bib25","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.jaci.2015.11.037","article-title":"The cardiomyocyte protein \u03b1T-catenin contributes to asthma through regulating pulmonary vein inflammation","volume":"138","author":"Folmsbee","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025021915034511500_bib26","doi-asserted-by":"publisher","first-page":"3936","DOI":"10.4049\/jimmunol.171.8.3936","article-title":"Prostaglandin D2 inhibits airway dendritic cell migration and function in steady state conditions by selective activation of the D prostanoid receptor 1","volume":"171","author":"Hammad","year":"2003","journal-title":"J. Immunol."},{"key":"2025021915034511500_bib27","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nature16985","article-title":"Visualization of immediate immune responses to pioneer metastatic cells in the lung","volume":"531","author":"Headley","year":"2016","journal-title":"Nature"},{"key":"2025021915034511500_bib28","doi-asserted-by":"publisher","first-page":"2268","DOI":"10.2337\/db15-1689","article-title":"CCR7 maintains nonresolving lymph node and adipose inflammation in obesity","volume":"65","author":"Hellmann","year":"2016","journal-title":"Diabetes"},{"key":"2025021915034511500_bib29","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1183\/09031936.00048509","article-title":"SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects","volume":"35","author":"Holz","year":"2010","journal-title":"Eur. Respir. J."},{"key":"2025021915034511500_bib30","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1016\/j.cell.2019.07.028","article-title":"Structural Basis for allosteric ligand recognition in the human CC chemokine receptor 7","volume":"178","author":"Jaeger","year":"2019","journal-title":"Cell"},{"key":"2025021915034511500_bib31","doi-asserted-by":"publisher","first-page":"5577","DOI":"10.1038\/s41598-017-06031-3","article-title":"Development and characterization of a novel Prox1-EGFP lymphatic and schlemm\u2019s canal reporter rat","volume":"7","author":"Jung","year":"2017","journal-title":"Sci. Rep."},{"key":"2025021915034511500_bib32","doi-asserted-by":"publisher","first-page":"239","DOI":"10.4049\/jimmunol.0901047","article-title":"T cell and APC dynamics in situ control the outcome of vaccination","volume":"185","author":"Khanna","year":"2010","journal-title":"J. Immunol."},{"key":"2025021915034511500_bib33","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.4049\/jimmunol.0901089","article-title":"Alveolar macrophages transport pathogens to lung draining lymph nodes","volume":"183","author":"Kirby","year":"2009","journal-title":"J. Immunol."},{"key":"2025021915034511500_bib34","doi-asserted-by":"publisher","first-page":"18073","DOI":"10.1073\/pnas.1008737107","article-title":"In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation","volume":"107","author":"Kreisel","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021915034511500_bib35","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1038\/ncomms2060","article-title":"Real-time in vivo imaging of the beating mouse heart at microscopic resolution","volume":"3","author":"Lee","year":"2012","journal-title":"Nat. Commun."},{"key":"2025021915034511500_bib36","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nature21706","article-title":"The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors","volume":"544","author":"Lefran\u00e7ais","year":"2017","journal-title":"Nature"},{"key":"2025021915034511500_bib37","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.98178","article-title":"Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury","volume":"3","author":"Lefran\u00e7ais","year":"2018","journal-title":"JCI Insight"},{"key":"2025021915034511500_bib38","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/mi.2012.30","article-title":"Lung transplant acceptance is facilitated by early events in the graft and is associated with lymphoid neogenesis","volume":"5","author":"Li","year":"2012","journal-title":"Mucosal Immunol."},{"key":"2025021915034511500_bib39","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax0428","article-title":"Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer","volume":"11","author":"Li","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"2025021915034511500_bib40","doi-asserted-by":"publisher","first-page":"111991","DOI":"10.1016\/j.celrep.2023.111991","article-title":"Glycosyltransferase Extl1 promotes CCR7-mediated dendritic cell migration to restrain infection and autoimmunity","volume":"42","author":"Liu","year":"2023","journal-title":"Cell Rep."},{"key":"2025021915034511500_bib41","doi-asserted-by":"publisher","first-page":"19083","DOI":"10.1073\/pnas.1905054116","article-title":"Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes","volume":"116","author":"Lok","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021915034511500_bib42","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nmeth.1543","article-title":"Stabilized imaging of immune surveillance in the mouse lung","volume":"8","author":"Looney","year":"2011","journal-title":"Nat. Methods"},{"key":"2025021915034511500_bib43","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aat4758","article-title":"Unexpected contribution of lymphatic vessels to promotion of distant metastatic tumor spread","volume":"4","author":"Ma","year":"2018","journal-title":"Sci. Adv."},{"key":"2025021915034511500_bib44","doi-asserted-by":"publisher","first-page":"6249","DOI":"10.1182\/bloodadvances.2022007798","article-title":"Lymphatic coagulation and neutrophil extracellular traps in lung-draining lymph nodes of COVID-19 decedents","volume":"6","author":"MacDonald","year":"2022","journal-title":"Blood Adv."},{"key":"2025021915034511500_bib45","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1189\/jlb.3HI0614-303R","article-title":"Chemokine receptor CCR7 regulates the intestinal TH1\/TH17\/Treg balance during Crohn\u2019s-like murine ileitis","volume":"97","author":"McNamee","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"2025021915034511500_bib46","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/dvg.20335","article-title":"A global double-fluorescent Cre reporter mouse","volume":"45","author":"Muzumdar","year":"2007","journal-title":"Genesis"},{"key":"2025021915034511500_bib47","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.cell.2020.08.020","article-title":"Patrolling alveolar macrophages conceal bacteria from the immune system to maintain homeostasis","volume":"183","author":"Neupane","year":"2020","journal-title":"Cell"},{"key":"2025021915034511500_bib48","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137377","article-title":"Lung megakaryocytes are immune modulatory cells","volume":"131","author":"Pariser","year":"2021","journal-title":"J. Clin. Invest."},{"key":"2025021915034511500_bib49","doi-asserted-by":"publisher","first-page":"1800786","DOI":"10.1183\/13993003.00786-2018","article-title":"Neutrophils disturb pulmonary microcirculation in sepsis-induced acute lung injury","volume":"53","author":"Park","year":"2019","journal-title":"Eur. Respir. J."},{"key":"2025021915034511500_bib50","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.cell.2004.10.010","article-title":"JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic stem cells","volume":"119","author":"Passegu\u00e9","year":"2004","journal-title":"Cell"},{"key":"2025021915034511500_bib51","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1152\/japplphysiol.00254.2005","article-title":"Effects of tidal volume and respiratory frequency on lung lymph flow","volume":"99","author":"Pearse","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"2025021915034511500_bib52","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw5075","article-title":"Lymphangiogenesis in kidney and lymph node mediates renal inflammation and fibrosis","volume":"5","author":"Pei","year":"2019","journal-title":"Sci. Adv."},{"key":"2025021915034511500_bib53","doi-asserted-by":"publisher","first-page":"7114","DOI":"10.1038\/ncomms8114","article-title":"Effector lymphocyte-induced lymph node-like vasculature enables naive T-cell entry into tumours and enhanced anti-tumour immunity","volume":"6","author":"Peske","year":"2015","journal-title":"Nat. Commun."},{"key":"2025021915034511500_bib54","doi-asserted-by":"publisher","first-page":"2925","DOI":"10.1084\/jem.20091739","article-title":"Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels","volume":"206","author":"Pflicke","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025021915034511500_bib55","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210409","article-title":"Marginating transitional B cells modulate neutrophils in the lung during inflammation and pneumonia","volume":"218","author":"Podstawka","year":"2021","journal-title":"J. Exp. Med."},{"key":"2025021915034511500_bib56","doi-asserted-by":"publisher","first-page":"2514","DOI":"10.1172\/JCI125044","article-title":"Lymphatic impairment leads to pulmonary tertiary lymphoid organ formation and alveolar damage","volume":"129","author":"Reed","year":"2019","journal-title":"J. Clin. Invest."},{"key":"2025021915034511500_bib57","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1164\/rccm.201405-0992OC","article-title":"CXCR2 antagonist MK-7123. A phase 2 proof-of-concept trial for chronic obstructive pulmonary disease","volume":"191","author":"Rennard","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025021915034511500_bib58","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1189\/jlb.1HI0415-149R","article-title":"Neutrophils rapidly transit inflamed lymphatic vessel endothelium via integrin-dependent proteolysis and lipoxin-induced junctional retraction","volume":"98","author":"Rigby","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"2025021915034511500_bib59","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.ccell.2020.05.002","article-title":"Visualizing synaptic transfer of tumor antigens among dendritic cells","volume":"37","author":"Ruhland","year":"2020","journal-title":"Cancer Cell"},{"key":"2025021915034511500_bib60","doi-asserted-by":"publisher","first-page":"2472","DOI":"10.4049\/jimmunol.162.5.2472","article-title":"Cutting edge: Secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes","volume":"162","author":"Saeki","year":"1999","journal-title":"J. Immunol."},{"key":"2025021915034511500_bib61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105429","article-title":"The MacBlue binary transgene (csf1r-gal4VP16\/UAS-ECFP) provides a novel marker for visualisation of subsets of monocytes, macrophages and dendritic cells and responsiveness to CSF1 administration","volume":"9","author":"Sauter","year":"2014","journal-title":"PLoS One"},{"key":"2025021915034511500_bib62","doi-asserted-by":"publisher","first-page":"L262","DOI":"10.1152\/ajplung.00046.2023","article-title":"Optimizing anesthesia and delivery approaches for dosing into lungs of mice","volume":"325","author":"Seo","year":"2023","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"2025021915034511500_bib63","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1126\/science.1185837","article-title":"Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21","volume":"328","author":"Shields","year":"2010","journal-title":"Science"},{"key":"2025021915034511500_bib64","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/s41590-023-01443-y","article-title":"T cell egress via lymphatic vessels is tuned by antigen encounter and limits tumor control","volume":"24","author":"Steele","year":"2023","journal-title":"Nat. Immunol."},{"key":"2025021915034511500_bib65","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192197","article-title":"Retrograde migration supplies resident memory T cells to lung-draining LN after influenza infection","volume":"217","author":"Stolley","year":"2020","journal-title":"J. Exp. Med."},{"key":"2025021915034511500_bib66","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1165\/rcmb.2016-0290TR","article-title":"Lymphatic changes in respiratory diseases: More than just remodeling of the lung?","volume":"57","author":"Stump","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2025021915034511500_bib67","doi-asserted-by":"publisher","first-page":"5012","DOI":"10.1038\/s41598-022-08617-y","article-title":"Lung lymphatic thrombosis and dysfunction caused by cigarette smoke exposure precedes emphysema in mice","volume":"12","author":"Summers","year":"2022","journal-title":"Sci. Rep."},{"key":"2025021915034511500_bib68","doi-asserted-by":"publisher","first-page":"3460","DOI":"10.1038\/s41467-021-23546-6","article-title":"Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema","volume":"12","author":"Sz\u0151ke","year":"2021","journal-title":"Nat. Commun."},{"key":"2025021915034511500_bib69","doi-asserted-by":"publisher","first-page":"5239","DOI":"10.1038\/s41467-022-32848-2","article-title":"An analysis modality for vascular structures combining tissue-clearing technology and topological data analysis","volume":"13","author":"Takahashi","year":"2022","journal-title":"Nat. Commun."},{"key":"2025021915034511500_bib70","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63296","article-title":"Bronchus-associated macrophages efficiently capture and present soluble inhaled antigens and are capable of local Th2 cell activation","volume":"11","author":"Tang","year":"2022","journal-title":"Elife"},{"key":"2025021915034511500_bib71","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1182\/blood-2006-04-020362","article-title":"Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo","volume":"109","author":"Tiedt","year":"2007","journal-title":"Blood"},{"key":"2025021915034511500_bib72","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.pupt.2016.09.005","article-title":"The effects of a CXCR1\/CXCR2 antagonist on neutrophil migration in mild atopic asthmatic subjects","volume":"41","author":"Todd","year":"2016","journal-title":"Pulm. Pharmacol. Ther."},{"key":"2025021915034511500_bib73","doi-asserted-by":"publisher","first-page":"1118583","DOI":"10.3389\/fmed.2023.1118583","article-title":"The lymphatic vasculature in lung function and respiratory disease","volume":"10","author":"Trivedi","year":"2023","journal-title":"Front. Med. (Lausanne)"},{"key":"2025021915034511500_bib74","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/s41586-020-2623-z","article-title":"Lymph protects metastasizing melanoma cells from ferroptosis","volume":"585","author":"Ubellacker","year":"2020","journal-title":"Nature"},{"key":"2025021915034511500_bib75","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1152\/ajplegacy.1942.136.1.207","article-title":"The flow of lymph from the lungs of the dog","volume":"136","author":"Warren","year":"1942","journal-title":"Am. J. Physiol."},{"key":"2025021915034511500_bib76","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1097\/CCM.0b013e3181ef4460","article-title":"The epidemiology of mechanical ventilation use in the United States","volume":"38","author":"Wunsch","year":"2010","journal-title":"Crit. Care Med."},{"key":"2025021915034511500_bib77","doi-asserted-by":"publisher","first-page":"20.1.1","DOI":"10.1002\/0471142735.im2001s108","article-title":"Mouse model for pre-clinical study of human cancer immunotherapy","volume":"108","author":"Ya","year":"2015","journal-title":"Curr. Protoc. Immunol."},{"key":"2025021915034511500_bib78","doi-asserted-by":"publisher","first-page":"6071","DOI":"10.4049\/jimmunol.1202798","article-title":"Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1","volume":"190","author":"Yamazaki","year":"2013","journal-title":"J. Immunol."},{"key":"2025021915034511500_bib79","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1161\/CIRCRESAHA.114.303119","article-title":"Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period","volume":"114","author":"Yao","year":"2014","journal-title":"Circ. Res."},{"key":"2025021915034511500_bib80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0272857","article-title":"Impact of protein identity on tumor-associated antigen uptake into infiltrating immune cells: A comparison of different fluorescent proteins as model antigens","volume":"17","author":"Yi","year":"2022","journal-title":"PLoS One"},{"key":"2025021915034511500_bib81","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1152\/jappl.1994.77.3.1294","article-title":"Removal of albumin microinjected in rat lung perimicrovascular space","volume":"77","author":"Ying","year":"1994","journal-title":"J. Appl. Physiol."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20241359\/1939056\/jem_20241359.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20241359\/1939056\/jem_20241359.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T10:12:00Z","timestamp":1739959920000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/222\/5\/e20241359\/277274\/Intravital-imaging-of-pulmonary-lymphatics-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":81,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5,5]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20241359","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.09.12.612619","asserted-by":"object"}]},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"article-number":"e20241359"}}