{"id":8247,"date":"2024-04-25T10:18:05","date_gmt":"2024-04-25T01:18:05","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=8247"},"modified":"2024-04-30T10:28:11","modified_gmt":"2024-04-30T01:28:11","slug":"ishii2024-4-22","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2024year\/ishii2024-4-22","title":{"rendered":"Yu Miyamoto,  Masaru Ishii \u226aImmunology and Regenerative Medicine\u226b <span>Identifying a new liver defender: The role of resident macrophages<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"https:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2024year\/ishii2024-4-22\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><span class=\"lineFrame\">Nature<\/span><\/p>\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-8248 size-medium\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig1-400x294.jpg?_t=1714091937\" alt=\"\" width=\"400\" height=\"294\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig1-400x294.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig1-768x564.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig1.jpg 850w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><\/a><br \/>Figure 1. &#8220;Sentinel macrophages&#8221; at the gateway of the liver phagocytose the gut-derived pathogens and produce the anti-inflammatory proteins, thereby suppressing surrounding inflammatory responses.<\/p>\n<div class=\"TextBlock\">\n<p>The liver and intestines are directly connected via the portal vein, a blood vessel that transports nutrients absorbed in the intestines directly to the liver. The intestines harbor numerous gut bacteria, and sometimes these bacteria and their related substances can enter the liver through the portal vein. This is especially problematic when the intestinal barrier is compromised, as seen in conditions like ulcerative colitis or leaky gut syndrome, allowing many gut bacteria and related substances to reach the liver. Under normal circumstances, the liver\u2019s immune system is able to defend against the invading gut bacteria and related substances and prevent inflammation, but the exact mechanism behind this was unclear.<\/p>\n<p>Using innovative technologies like <em>in vivo<\/em> imaging of the liver and analysis of single-cell gene expression while preserving tissue locational information, a research group led by Yu Miyamoto and Masaru Ishii at the Graduate School of Medicine of Osaka University has revealed that certain resident macrophages near the entrance of the liver protect it against intestinal bacteria and related substances. Their findings are illustrated in Figure 1. Dr. Miyamoto, a lead author of the study, explained, \u201cOur technology showed that these \u2018sentinel macrophages\u2019 play a crucial role in protecting the liver from inflammation caused by intestinal bacteria and related substances.&#8221; Additionally, the study found that isoallo-lithocholic acid (isoallo-LCA), a secondary bile acid produced by some gut bacteria, trigger the activation of these sentinel macrophages.<\/p>\n<p>With the rise in conditions like leaky gut due to modern lifestyles (stress, high-fat diets, and lack of exercise), there is increasing concern about inflammation affecting various organs, including the liver. Metabolic dysfunction-associated steatohepatitis (MASH), often accompanied by the leaky gut, has been particularly concerning due to its ever increasing incidence and challenging treatment. This research shed light on how liver sentinel macrophages defend against gut commensal invaders, offering hope that enhancing their functions could lead to the development of new preventive and therapeutic strategies for liver chronic inflammatory diseases, including MASH.<\/p>\n<\/div>\n<p>###<\/p>\n<p>The article, \u201cPeriportal macrophages protect against commensal-driven liver inflammation\u201d was published in <em>Nature<\/em> at DOI: <a href=\"https:\/\/www.nature.com\/articles\/s41586-024-07372-6\">https:\/\/www.nature.com\/articles\/s41586-024-07372-6<\/a>.<\/p>\n<p><strong>Summary:<\/strong> Osaka University researchers discovered liver resident macrophages&#8217; pivotal role in defending against gut bacteria and related substances entering via the portal vein, particularly under compromised intestinal barrier conditions. Identified as &#8220;sentinel macrophages,&#8221; they are activated by isoallo-lithocholic acid. This finding holds promise for developing preventive and therapeutic strategies for liver chronic inflammatory diseases, such as metabolic dysfunction-associated steatohepatitis (MASH), by enhancing the function of these macrophages to mitigate inflammation and improve treatment efficacy.<\/p>\n<p><strong>Primary Keyword<\/strong>: Health and medicine<\/p>\n<p><strong>Method of Research<\/strong>: Imaging analysis<\/p>\n<p><strong>Subject of Research<\/strong>: Animals<\/p>\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig2.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-8254 size-medium\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig2-400x156.jpg?_t=1714092657\" alt=\"\" width=\"400\" height=\"156\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig2-400x156.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig2-768x300.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig2.jpg 1000w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><\/a><br \/>Figure 2. Abundance of the \u201cliver sentinel macrophages\u201d in normal and disease human livers. The livers from metabolic dysfunction-associated fatty liver disease (MAFLD, less severe) and steatohepatitis (MASH, severe) were shown as the disease livers. Green: Sentinel macrophages, Red: Other normal macrophages, Cyan: Bile duct. Scale bar: 100 \u00b5m. Quantitative data are presented as the means (asterisk) with medians, smallest observations, lower and upper quartiles, and largest observations.<\/p>\n<div class=\"TextBlock\">\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig3.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-8255 size-medium\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig3-400x273.jpg?_t=1714092695\" alt=\"\" width=\"400\" height=\"273\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig3-400x273.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig3-768x525.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2024\/04\/ishii_efig3.jpg 850w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><\/a><br \/>Figure 3. Induction of the liver sentinel macrophages by isoallo-lithocholic acids (isoallo-LCA). Abundance of \u201csentinel macrophages\u201d in the liver (A) and expression level of the anti-inflammatory cytokine IL-10 in liver resident macrophages (B) two weeks after daily oral administration of isoallo-LCA or vehicle control. Data are presented as the means (asterisk) with medians, smallest observations, lower and upper quartiles, and largest observations.<\/p>\n<\/div>\n<div class=\"TextBlock\">\n<p>Title: \u201cPeriportal macrophages protect against commensal-driven liver inflammation\u201d<\/p>\n<\/div>\n<p>Journal: <em>Nature<\/em><em><br \/><\/em>Authors: Yu Miyamoto, Junichi Kikuta, Takahiro Matsui, Tetsuo Hasegawa, Kentaro Fujii, Daisuke Okuzaki, Yu-chen Liu, Takuya Yoshioka, Shigeto Seno, Daisuke Motooka, Yutaka Uchida, Erika Yamashita, Shogo Kobayashi, Hidetoshi Eguchi, Eiichi Morii, Karl Tryggvason, Takashi Shichita, Hisako Kayama, Koji Atarashi, Jun Kunisawa, Kenya Honda, Kiyoshi Takeda &amp; Masaru Ishii.<br \/>DOI: <a href=\"https:\/\/www.nature.com\/articles\/s41586-024-07372-6\">10.1038\/s41586-024-07372-6<\/a><\/p>\n<p>Japan Society for the Promotion of Science (JSPS)<br \/>Japan Agency for Medical Research and Development (AMED)<br \/>Japan Science and Technology Agency (JST)<br \/>Uehara Memorial Foundation<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Nature Figure 1. &#8220;Sentinel macrophages&#8221; at the gateway of the liver phagocytose t [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":8248,"parent":8108,"menu_order":32,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8247"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=8247"}],"version-history":[{"count":8,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8247\/revisions"}],"predecessor-version":[{"id":8265,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8247\/revisions\/8265"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8108"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/8248"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=8247"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}