{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:54:30Z","timestamp":1787316870455,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:00:00Z","timestamp":1692662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K07438"],"award-info":[{"award-number":["JP20K07438"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21H03038"],"award-info":[{"award-number":["JP21H03038"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Pt A"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Liver macrophages are critical components of systemic immune system defense mechanisms. F4\/80\n                    <jats:sup>high<\/jats:sup>\n                    Kupffer cells (KCs) are the predominant liver\u2010resident macrophages and the first immune cells to contact pathogens entering the liver. F4\/80\n                    <jats:sup>low<\/jats:sup>\n                    monocyte\u2010derived macrophages (MoM\u03c6s) are essential macrophages that modulate liver immune functions. Here we report a novel method of identifying subpopulations of these two populations using traditional flow cytometry and examine each subpopulation for its putative roles in the pathogenesis of an experimental non\u2010alcoholic steatohepatitis model. Using male C57BL\/6 mice, we isolated and analyzed liver non\u2010parenchymal cells by flow cytometry. We identified F4\/80\n                    <jats:sup>high<\/jats:sup>\n                    and F4\/80\n                    <jats:sup>low<\/jats:sup>\n                    macrophage populations and characterized subpopulations using uniform manifold approximation and projection. We identified three subpopulations in F4\/80\n                    <jats:sup>high<\/jats:sup>\n                    macrophages: CD163(+) KCs, CD163(\u2212) KCs, and liver capsular macrophages. CD163(+) KCs had higher phagocytic and bactericidal activities and more complex cellular structures than CD163(\u2212) KCs. We also identified four subpopulations of F4\/80\n                    <jats:sup>low<\/jats:sup>\n                    MoM\u03c6s based on Ly6C and MHC class II expression: infiltrating monocytes, pro\u2010inflammatory MoM\u03c6s, Ly6C(\u2212) monocytes, and conventional dendritic cells. CCR2 knock\u2010out mice expressed lower levels of these monocyte\u2010derived cells, and the count varied by subpopulation. In high\u2010fat\u2010 and cholesterol\u2010diet\u2010fed mice, only one subpopulation, pro\u2010inflammatory MoM\u03c6s, significantly increased in count. This indicates that changes to this subpopulation is the first step in the progression to non\u2010alcoholic steatohepatitis. The community can use our novel subpopulation and gating strategy to better understand complex immunological mechanisms in various liver disorders through detailed analysis of these subpopulations.\n                  <\/jats:p>","DOI":"10.1002\/cyto.a.24783","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T12:52:10Z","timestamp":1692708730000},"page":"902-914","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel phenotypical and functional sub\u2010classification of liver macrophages highlights changes in population dynamics in experimental mouse models"],"prefix":"10.1002","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6066-3031","authenticated-orcid":false,"given":"Hiroyuki","family":"Nakashima","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology National Defense Medical College  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley M.","family":"Kearney","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology National Defense Medical College  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azusa","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology National Defense Medical College  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Division of Biomedical Engineering National Defense Medical College Research Institute  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seigo","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Self\u2010Defense Force Iruma Hospital  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology National Defense Medical College  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology National Defense Medical College  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.200"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0528.2002.017404.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02933897"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.52.1.159"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.110.1.27"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.06.002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.132.3.521"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.12.025"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.04.037"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049339"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep34466"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092515"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2020.113951"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2011.02667.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.990090809"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.3.3.295-300.1996"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.24213"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpcy.70"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142956.cy0127s63"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/07388551.2015.1128876"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254886"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00982.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00558-8"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.003"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.07.018"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2008.0027"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(89)90178-6"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.05.005"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.08.006"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-5926-2-S1-S2"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100831"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.1TA0517-169R"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25906"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2017.10.006"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830111013"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2017.02.076"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15630"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-020-03324-2"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15877"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082163"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e31822dc6e4"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1159\/000475931"}],"container-title":["Cytometry 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