Periportal macrophages protect against commensal-driven liver inflammation

Miyamoto, Yu; Kikuta, Junichi; Matsui, Takahiro; Hasegawa, Tetsuo; Fujii, Kentaro; Okuzaki, Daisuke; Liu, Yu Chen; Yoshioka, Takuya; Seno, Shigeto; Motooka, Daisuke; Uchida, Yutaka; Yamashita, Erika; Kobayashi, Shogo; Eguchi, Hidetoshi; Morii, Eiichi; Tryggvason, Karl; Shichita, Takashi; Kayama, Hisako; Atarashi, Koji; Kunisawa, Jun; Honda, Kenya; Takeda, Kiyoshi; Ishii, Masaru

doi:https://doi.org/10.1038/s41586-024-07372-6

Periportal macrophages protect against commensal-driven liver inflammation

Miyamoto, Yu; Kikuta, Junichi; Matsui, Takahiro et al.

Nature, 2024, 629, 901-909

アクセス数:86件（2025-03-18 14:18 集計）

固定URL: https://hdl.handle.net/11094/95817

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Nature_629_901	pdf	なし	4.28 MB	16	2024.11.23

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タイトル	Periportal macrophages protect against commensal-driven liver inflammation
著者	NRID 1000090965336 1000090965336 researchmap permalink yumiyamoto yumiyamoto ORCID 0000-0002-2715-6465 0000-0002-2715-6465 著者名 Miyamoto, Yu
	NRID 1000060710069 1000060710069 researchmap permalink jkikuta jkikuta Scopus Author ID 36637603800 36637603800 著者名 Kikuta, Junichi
	NRID 1000050747037 1000050747037 ORCID 0000-0002-6753-1688 0000-0002-6753-1688 researchmap permalink takahiromatsui takahiromatsui Scopus Author ID 35176152500 35176152500 著者名 Matsui, Takahiro
	NRID 1000030773048 1000030773048 著者名 Hasegawa, Tetsuo
	NRID 1000090908328 1000090908328 researchmap permalink u730550d u730550d Scopus Author ID 57201556508 57201556508 著者名 Fujii, Kentaro
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 著者名 Okuzaki, Daisuke
	NRID 1000050894698 1000050894698 ORCID 0000-0002-2750-0182 0000-0002-2750-0182 researchmap permalink liuyuchen liuyuchen 著者名 Liu, Yu Chen
	著者名 Yoshioka, Takuya
	NRID 1000030432462 1000030432462 ORCID 0000-0003-3861-6444 0000-0003-3861-6444 researchmap permalink ssenoo ssenoo Scopus Author ID 57214748425 57214748425 著者名 Seno, Shigeto
	NRID 1000010636830 1000010636830 researchmap permalink daisukem daisukem Scopus Author ID 35315737900 35315737900 著者名 Motooka, Daisuke
	NRID 1000050833787 1000050833787 researchmap permalink YutakaUchida YutakaUchida Scopus Author ID 56967526600 56967526600 著者名 Uchida, Yutaka
	NRID 1000010880106 1000010880106 ORCID 0000-0002-3973-9529 0000-0002-3973-9529 researchmap permalink erika-ys erika-ys 著者名 Yamashita, Erika
	NRID 1000030452436 1000030452436 researchmap permalink 30452436 30452436 Scopus Author ID 7405376089 7405376089 ORCID 0000-0002-8828-1067 0000-0002-8828-1067 著者名 Kobayashi, Shogo
	NRID 1000090542118 1000090542118 researchmap permalink abcdabcdabcd abcdabcdabcd Scopus Author ID 7101627772 7101627772 著者名 Eguchi, Hidetoshi
	NRID 1000010283772 1000010283772 ORCID 0000-0001-8490-3650 0000-0001-8490-3650 researchmap permalink read0046454 read0046454 Scopus Author ID 7003914326 7003914326 著者名 Morii, Eiichi
	著者名 Tryggvason, Karl
	NRID 1000000598443 1000000598443 著者名 Shichita, Takashi
	NRID 1000040548814 1000040548814 researchmap permalink 0425Kayama_Hisako 0425Kayama_Hisako Scopus Author ID 24390899100 24390899100 著者名 Kayama, Hisako
	NRID 1000060546787 1000060546787 著者名 Atarashi, Koji
	NRID 1000080376615 1000080376615 著者名 Kunisawa, Jun
	NRID 1000060334231 1000060334231 著者名 Honda, Kenya
	NRID 1000020309446 1000020309446 ORCID 0000-0002-1778-6332 0000-0002-1778-6332 researchmap permalink read0118278 read0118278 Scopus Author ID 7404335442 7404335442 著者名 Takeda, Kiyoshi
	NRID 1000010324758 1000010324758 researchmap permalink read0076684 read0076684 Scopus Author ID 35074093500 35074093500 著者名 Ishii, Masaru
内容	Miyamoto Y., Kikuta J., Matsui T., et al. Periportal macrophages protect against commensal-driven liver inflammation. Nature 629, 901 (2024); https://doi.org/10.1038/s41586-024-07372-6.
抄録	The liver is the main gateway from the gut, and the unidirectional sinusoidal flow from portal to central veins constitutes heterogenous zones, including the periportal vein (PV) and the pericentral vein zones1–5. However, functional differences in the immune system in each zone remain poorly understood. Here intravital imaging revealed that inflammatory responses are suppressed in PV zones. Zone-specific single-cell transcriptomics detected a subset of immunosuppressive macrophages enriched in PV zones that express high levels of interleukin-10 and Marco, a scavenger receptor that sequesters pro-inflammatory pathogen-associated molecular patterns and damage-associated molecular patterns, and consequently suppress immune responses. Induction of Marco⁺ immunosuppressive macrophages depended on gut microbiota. In particular, a specific bacterial family, Odoribacteraceae, was identified to induce this macrophage subset through its postbiotic isoallolithocholic acid. Intestinal barrier leakage resulted in inflammation in PV zones, which was markedly augmented in Marco-deficient conditions. Chronic liver inflammatory diseases such as primary sclerosing cholangitis (PSC) and non-alcoholic steatohepatitis (NASH) showed decreased numbers of Marco⁺ macrophages. Functional ablation of Marco⁺ macrophages led to PSC-like inflammatory phenotypes related to colitis and exacerbated steatosis in NASH in animal experimental models. Collectively, commensal bacteria induce Marco⁺ immunosuppressive macrophages, which consequently limit excessive inflammation at the gateway of the liver. Failure of this self-limiting system promotes hepatic inflammatory disorders such as PSC and NASH.
出版者	Nature Research
収録物名	Nature
巻(号)	629
ページ	901-909
刊行年月	2024-05-23
言語	英語
ハンドルURL	https://hdl.handle.net/11094/95817
PISSN	00280836
eISSN	14764687
関連情報 (isVersionOf)	DOI (出版社版) https://doi.org/10.1038/s41586-024-07372-6
アクセス権	open access
出版タイプ	Accepted Manuscript
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Nature. 2024, 629, p. 901-909
DC.title	Periportal macrophages protect against commensal-driven liver inflammation
DC.creator	Miyamoto, Yu
	Kikuta, Junichi
	Matsui, Takahiro
	Hasegawa, Tetsuo
	Fujii, Kentaro
	Okuzaki, Daisuke
	Liu, Yu Chen
	Yoshioka, Takuya
	Seno, Shigeto
	Motooka, Daisuke
	Uchida, Yutaka
	Yamashita, Erika
	Kobayashi, Shogo
	Eguchi, Hidetoshi
	Morii, Eiichi
	Tryggvason, Karl
	Shichita, Takashi
	Kayama, Hisako
	Atarashi, Koji
	Kunisawa, Jun
	Honda, Kenya
	Takeda, Kiyoshi
	Ishii, Masaru
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-05-23
DC.identifier	https://doi.org/10.1038/s41586-024-07372-6
DC.description	Miyamoto Y., Kikuta J., Matsui T., et al. Periportal macrophages protect against commensal-driven liver inflammation. Nature 629, 901 (2024); https://doi.org/10.1038/s41586-024-07372-6.
DCTERMS.abstract	The liver is the main gateway from the gut, and the unidirectional sinusoidal flow from portal to central veins constitutes heterogenous zones, including the periportal vein (PV) and the pericentral vein zones1–5. However, functional differences in the immune system in each zone remain poorly understood. Here intravital imaging revealed that inflammatory responses are suppressed in PV zones. Zone-specific single-cell transcriptomics detected a subset of immunosuppressive macrophages enriched in PV zones that express high levels of interleukin-10 and Marco, a scavenger receptor that sequesters pro-inflammatory pathogen-associated molecular patterns and damage-associated molecular patterns, and consequently suppress immune responses. Induction of Marco⁺ immunosuppressive macrophages depended on gut microbiota. In particular, a specific bacterial family, Odoribacteraceae, was identified to induce this macrophage subset through its postbiotic isoallolithocholic acid. Intestinal barrier leakage resulted in inflammation in PV zones, which was markedly augmented in Marco-deficient conditions. Chronic liver inflammatory diseases such as primary sclerosing cholangitis (PSC) and non-alcoholic steatohepatitis (NASH) showed decreased numbers of Marco⁺ macrophages. Functional ablation of Marco⁺ macrophages led to PSC-like inflammatory phenotypes related to colitis and exacerbated steatosis in NASH in animal experimental models. Collectively, commensal bacteria induce Marco⁺ immunosuppressive macrophages, which consequently limit excessive inflammation at the gateway of the liver. Failure of this self-limiting system promotes hepatic inflammatory disorders such as PSC and NASH.
DC.format	95817
citation_title	Periportal macrophages protect against commensal-driven liver inflammation
citation_author	Miyamoto, Yu
	Kikuta, Junichi
	Matsui, Takahiro
	Hasegawa, Tetsuo
	Fujii, Kentaro
	Okuzaki, Daisuke
	Liu, Yu Chen
	Yoshioka, Takuya
	Seno, Shigeto
	Motooka, Daisuke
	Uchida, Yutaka
	Yamashita, Erika
	Kobayashi, Shogo
	Eguchi, Hidetoshi
	Morii, Eiichi
	Tryggvason, Karl
	Shichita, Takashi
	Kayama, Hisako
	Atarashi, Koji
	Kunisawa, Jun
	Honda, Kenya
	Takeda, Kiyoshi
	Ishii, Masaru
citation_publisher	Nature Research
citation_language	英語
citation_date	2024-05-23
citation_journal_title	Nature
citation_volume	629
citation_firstpage	901
citation_lastpage	909
citation_doi	https://doi.org/10.1038/s41586-024-07372-6
citation_public_url	https://hdl.handle.net/11094/95817

Periportal macrophages protect against commensal-driven liver inflammation

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