The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation

Liu, Li; Ito, Takayoshi; Li, Bo; Tani, Haruka; Okuzaki, Daisuke; Motooka, Daisuke; Miyazaki, Hazuki; Ogino, Takayuki; Nakamura, Shota; Takeda, Kiyoshi; Kayama, Hisako

doi:https://doi.org/10.1093/intimm/dxad050

The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation

Liu, Li; Ito, Takayoshi; Li, Bo et al.

International Immunology, 2024, 36(4), 155-166

Number of Access:1,858（2025-09-06 08:21 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/95386

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Title	The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation
Creator	NRID 1000050380093 1000050380093 researchmap permalink 7000008694 7000008694 Scopus Author ID 55628530013 55628530013 CreatorName Liu, Li
	CreatorName Ito, Takayoshi
	CreatorName Li, Bo
	CreatorName Tani, Haruka
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 CreatorName Okuzaki, Daisuke
	NRID 1000010636830 1000010636830 researchmap permalink daisukem daisukem Scopus Author ID 35315737900 35315737900 CreatorName Motooka, Daisuke
	CreatorName Miyazaki, Hazuki
	NRID 1000050597458 1000050597458 researchmap permalink togino04 togino04 Scopus Author ID 57200254430 57200254430 ORCID 0000-0001-5435-4144 0000-0001-5435-4144 CreatorName Ogino, Takayuki
	NRID 1000090432434 1000090432434 ORCID 0000-0003-2058-5942 0000-0003-2058-5942 researchmap permalink nkmrshota nkmrshota Scopus Author ID 35315778200 35315778200 CreatorName Nakamura, Shota
	NRID 1000020309446 1000020309446 ORCID 0000-0002-1778-6332 0000-0002-1778-6332 researchmap permalink read0118278 read0118278 Scopus Author ID 7404335442 7404335442 CreatorName Takeda, Kiyoshi
	NRID 1000040548814 1000040548814 researchmap permalink 0425Kayama_Hisako 0425Kayama_Hisako Scopus Author ID 24390899100 24390899100 CreatorName Kayama, Hisako
Subject	apoptosis
	eosinophilia
	ERK1/2
	ulcerative colitis
Description	This is a pre-copyedited, author-produced version of an article accepted for publication in International Immunology following peer review. The version of record Liu L., Ito T., Li B., et al. The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation. International Immunology 36, 155 (2024); is available online at: https://doi.org/10.1093/intimm/dxad050.
Abstract	Ulcerative colitis (UC) is a chronic disorder of the large intestine with inflammation and ulceration. The incidence and prevalence of UC have been rapidly increasing worldwide, but its etiology remains unknown. In patients with UC, the accumulation of eosinophils in the large intestinal mucosa is associated with increased disease activity. However, the molecular mechanism underlying the promotion of intestinal eosinophilia in patients with UC remains poorly understood. Here, we show that uridine diphosphate (UDP)-glucose mediates the eosinophil-dependent promotion of colonic inflammation via the purinergic receptor P2Y14. The expression of P2RY14 mRNA was upregulated in the large intestinal mucosa of patients with UC. The P2Y14 receptor ligand UDP-glucose was increased in the large intestinal tissue of mice administered dextran sodium sulfate (DSS). In addition, P2ry14 deficiency and P2Y14 receptor blockade mitigated DSS-induced colitis. Among the large intestinal immune cells and epithelial cells, eosinophils highly expressed P2ry14 mRNA. P2ry14-/- mice transplanted with wild-type bone marrow eosinophils developed more severe DSS-induced colitis compared with P2ry14-/- mice that received P2ry14-deficient eosinophils. UDP-glucose prolonged the lifespan of eosinophils and promoted gene transcription in the cells through P2Y14 receptor-mediated activation of ERK1/2 signaling. Thus, the UDP-glucose/P2Y14 receptor axis aggravates large intestinal inflammation by accelerating the accumulation and activation of eosinophils.
Publisher	Oxford University Press
Source Title	International Immunology
Volume (Issue)	36(4)
Page	155-166
Date of Issued	2024-04-04
Language	English
Handle URL	https://hdl.handle.net/11094/95386
PISSN	09538178
eISSN	14602377
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1093/intimm/dxad050
Access Rights	open access
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	International Immunology. 2024, 36(4), p. 155-166
DC.title	The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation
DC.creator	Liu, Li
	Ito, Takayoshi
	Li, Bo
	Tani, Haruka
	Okuzaki, Daisuke
	Motooka, Daisuke
	Miyazaki, Hazuki
	Ogino, Takayuki
	Nakamura, Shota
	Takeda, Kiyoshi
	Kayama, Hisako
DC.publisher	Oxford University Press
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-04-04
DC.identifier	https://doi.org/10.1093/intimm/dxad050
DC.subject	apoptosis
	eosinophilia
	ERK1/2
	ulcerative colitis
DC.description	This is a pre-copyedited, author-produced version of an article accepted for publication in International Immunology following peer review. The version of record Liu L., Ito T., Li B., et al. The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation. International Immunology 36, 155 (2024); is available online at: https://doi.org/10.1093/intimm/dxad050.
DCTERMS.abstract	Ulcerative colitis (UC) is a chronic disorder of the large intestine with inflammation and ulceration. The incidence and prevalence of UC have been rapidly increasing worldwide, but its etiology remains unknown. In patients with UC, the accumulation of eosinophils in the large intestinal mucosa is associated with increased disease activity. However, the molecular mechanism underlying the promotion of intestinal eosinophilia in patients with UC remains poorly understood. Here, we show that uridine diphosphate (UDP)-glucose mediates the eosinophil-dependent promotion of colonic inflammation via the purinergic receptor P2Y14. The expression of P2RY14 mRNA was upregulated in the large intestinal mucosa of patients with UC. The P2Y14 receptor ligand UDP-glucose was increased in the large intestinal tissue of mice administered dextran sodium sulfate (DSS). In addition, P2ry14 deficiency and P2Y14 receptor blockade mitigated DSS-induced colitis. Among the large intestinal immune cells and epithelial cells, eosinophils highly expressed P2ry14 mRNA. P2ry14-/- mice transplanted with wild-type bone marrow eosinophils developed more severe DSS-induced colitis compared with P2ry14-/- mice that received P2ry14-deficient eosinophils. UDP-glucose prolonged the lifespan of eosinophils and promoted gene transcription in the cells through P2Y14 receptor-mediated activation of ERK1/2 signaling. Thus, the UDP-glucose/P2Y14 receptor axis aggravates large intestinal inflammation by accelerating the accumulation and activation of eosinophils.
DC.format	95386
citation_title	The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation
citation_author	Liu, Li
	Ito, Takayoshi
	Li, Bo
	Tani, Haruka
	Okuzaki, Daisuke
	Motooka, Daisuke
	Miyazaki, Hazuki
	Ogino, Takayuki
	Nakamura, Shota
	Takeda, Kiyoshi
	Kayama, Hisako
citation_publisher	Oxford University Press
citation_language	English
citation_date	2024-04-04
citation_journal_title	International Immunology
citation_volume	36
citation_issue	4
citation_firstpage	155
citation_lastpage	166
citation_doi	https://doi.org/10.1093/intimm/dxad050
citation_public_url	https://hdl.handle.net/11094/95386

The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation

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