The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells

Oguro-Igashira, Eri; Murakami, Mari; Mori, Ryota; Kuwahara, Ryuichi; Kihara, Takako; Kohara, Masaharu; Fujiwara, Makoto; Motooka, Daisuke; Okuzaki, Daisuke; Arase, Mitsuru; Toyota, Hironobu; Peng, Siyun; Ogino, Takayuki; Kitabatake, Yasuji; Morii, Eiichi; Hirota, Seiichi; Ikeuchi, Hiroki; Umemoto, Eiji; Kumanogoh, Atsushi; Takeda, Kiyoshi

doi:https://doi.org/10.1073/pnas.2318767121

The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells

Oguro-Igashira, Eri; Murakami, Mari; Mori, Ryota et al.

Proceedings of the National Academy of Sciences of the United States of America, 2024, 121(44), e2318767121

アクセス数:29件（2025-03-18 17:21 集計）

固定URL: https://hdl.handle.net/11094/98561

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タイトル	The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells
著者	NRID 1000051004139 1000051004139 researchmap permalink 51004139 51004139 著者名 Oguro-Igashira, Eri
	NRID 1000010801293 1000010801293 ORCID 0000-0001-6458-8235 0000-0001-6458-8235 researchmap permalink marim marim Scopus Author ID 37100058000 37100058000 著者名 Murakami, Mari
	著者名 Mori, Ryota
	NRID 1000090839010 1000090839010 著者名 Kuwahara, Ryuichi
	NRID 1000000815889 1000000815889 著者名 Kihara, Takako
	ORCID 0009-0006-7636-5833 0009-0006-7636-5833 著者名 Kohara, Masaharu
	NRID 1000050625697 1000050625697 ORCID 0000-0002-6799-9774 0000-0002-6799-9774 researchmap permalink makofuji1977 makofuji1977 Scopus Author ID 57203794801 57203794801 著者名 Fujiwara, Makoto
	NRID 1000010636830 1000010636830 researchmap permalink daisukem daisukem Scopus Author ID 35315737900 35315737900 著者名 Motooka, Daisuke
	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
	著者名 Arase, Mitsuru
	著者名 Toyota, Hironobu
	著者名 Peng, Siyun
	NRID 1000050597458 1000050597458 researchmap permalink togino04 togino04 Scopus Author ID 57200254430 57200254430 著者名 Ogino, Takayuki
	NRID 1000080506494 1000080506494 ORCID 0000-0002-2907-9512 0000-0002-2907-9512 researchmap permalink kyasuji kyasuji Scopus Author ID 7003894272 7003894272 著者名 Kitabatake, Yasuji
	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
	NRID 1000050218856 1000050218856 著者名 Hirota, Seiichi
	NRID 1000080319863 1000080319863 著者名 Ikeuchi, Hiroki
	NRID 1000090452440 1000090452440 著者名 Umemoto, Eiji
	NRID 1000010294125 1000010294125 researchmap permalink read0051725 read0051725 Scopus Author ID 6602726311 6602726311 ORCID 0000-0003-4749-7117 0000-0003-4749-7117 著者名 Kumanogoh, Atsushi
	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
キーワード等	antigen recognition
	dendritic cell
	G protein-coupled receptors
	GPR31
	transepithelial dendrite formation
内容	Oguro-Igashira E., Murakami M., Mori R., et al. The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 121, e2318767121 (2024); https://doi.org/10.1073/pnas.2318767121.
抄録	The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe–GPCR interactions on human physiology have not been fully elucidated. Here, we show that GPR31, which is activated by the gut bacterial metabolite pyruvate, is specifically expressed on type 1 conventional dendritic cells (cDC1s) in the lamina propria of the human intestine. Using human induced pluripotent stem cell-derived cDC1s and a monolayer human gut organoid coculture system, we show that cDC1s extend their dendrites toward pyruvate on the luminal side, forming transepithelial dendrites (TED). Accordingly, GPR31 activation via pyruvate enhances the fundamental function of cDC1 by allowing efficient uptake of gut luminal antigens, such as dietary compounds and bacterial particles through TED formation. Our results highlight the role of GPCRs in tuning the human gut immune system according to local metabolic cues.
出版者	National Academy of Sciences
収録物名	Proceedings of the National Academy of Sciences of the United States of America
巻(号)	121(44)
ページ	e2318767121
刊行年月	2024-10-29
言語	英語
ハンドルURL	https://hdl.handle.net/11094/98561
PISSN	00278424
eISSN	10916490
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1073/pnas.2318767121
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
出版タイプ	Version of Record
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
DCTERMS.bibliographicCitation	Proceedings of the National Academy of Sciences of the United States of America. 2024, 121(44), p. e2318767121
DC.title	The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells
DC.creator	Oguro-Igashira, Eri
	Murakami, Mari
	Mori, Ryota
	Kuwahara, Ryuichi
	Kihara, Takako
	Kohara, Masaharu
	Fujiwara, Makoto
	Motooka, Daisuke
	Okuzaki, Daisuke
	Arase, Mitsuru
	Toyota, Hironobu
	Peng, Siyun
	Ogino, Takayuki
	Kitabatake, Yasuji
	Morii, Eiichi
	Hirota, Seiichi
	Ikeuchi, Hiroki
	Umemoto, Eiji
	Kumanogoh, Atsushi
	Takeda, Kiyoshi
DC.publisher	National Academy of Sciences
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-10-29
DC.identifier	https://doi.org/10.1073/pnas.2318767121
DC.subject	antigen recognition
	dendritic cell
	G protein-coupled receptors
	GPR31
	transepithelial dendrite formation
DC.description	Oguro-Igashira E., Murakami M., Mori R., et al. The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 121, e2318767121 (2024); https://doi.org/10.1073/pnas.2318767121.
DCTERMS.abstract	The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe–GPCR interactions on human physiology have not been fully elucidated. Here, we show that GPR31, which is activated by the gut bacterial metabolite pyruvate, is specifically expressed on type 1 conventional dendritic cells (cDC1s) in the lamina propria of the human intestine. Using human induced pluripotent stem cell-derived cDC1s and a monolayer human gut organoid coculture system, we show that cDC1s extend their dendrites toward pyruvate on the luminal side, forming transepithelial dendrites (TED). Accordingly, GPR31 activation via pyruvate enhances the fundamental function of cDC1 by allowing efficient uptake of gut luminal antigens, such as dietary compounds and bacterial particles through TED formation. Our results highlight the role of GPCRs in tuning the human gut immune system according to local metabolic cues.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	98561
citation_title	The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells
citation_author	Oguro-Igashira, Eri
	Murakami, Mari
	Mori, Ryota
	Kuwahara, Ryuichi
	Kihara, Takako
	Kohara, Masaharu
	Fujiwara, Makoto
	Motooka, Daisuke
	Okuzaki, Daisuke
	Arase, Mitsuru
	Toyota, Hironobu
	Peng, Siyun
	Ogino, Takayuki
	Kitabatake, Yasuji
	Morii, Eiichi
	Hirota, Seiichi
	Ikeuchi, Hiroki
	Umemoto, Eiji
	Kumanogoh, Atsushi
	Takeda, Kiyoshi
citation_publisher	National Academy of Sciences
citation_language	英語
citation_date	2024-10-29
citation_journal_title	Proceedings of the National Academy of Sciences of the United States of America
citation_volume	121
citation_issue	44
citation_firstpage	e2318767121
citation_doi	https://doi.org/10.1073/pnas.2318767121
citation_public_url	https://hdl.handle.net/11094/98561

The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells

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