Group 1 innate lymphoid cells and inflammatory macrophages exacerbate fibrosis in creeping fat through IFN-γ secretion

Mori, Ryota; Ogino, Takayuki; Murakami, Mari; Kayama, Hisako; Okuzaki, Daisuke; Ikeda, Atsuyo; Sekido, Yuki; Hata, Tsuyoshi; Hamabe, Atsushi; Takahashi, Hidekazu; Miyoshi, Norikatsu; Uemura, Mamoru; Ikeuchi, Hiroki; Takeda, Kiyoshi; Mizushima, Tsunekazu; Doki, Yuichiro; Eguchi, Hidetoshi

doi:https://doi.org/10.1007/s00535-025-02243-x

Group 1 innate lymphoid cells and inflammatory macrophages exacerbate fibrosis in creeping fat through IFN-γ secretion

Mori, Ryota; Ogino, Takayuki; Murakami, Mari et al.

Journal of Gastroenterology, 2025

Number of Access:1,749（2025-08-14 15:05 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/101112

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Title	Group 1 innate lymphoid cells and inflammatory macrophages exacerbate fibrosis in creeping fat through IFN-γ secretion
Creator	CreatorName Mori, Ryota
	NRID 1000050597458 1000050597458 researchmap permalink togino04 togino04 Scopus Author ID 57200254430 57200254430 CreatorName Ogino, Takayuki
	NRID 1000010801293 1000010801293 ORCID 0000-0001-6458-8235 0000-0001-6458-8235 researchmap permalink marim marim Scopus Author ID 37100058000 37100058000 CreatorName Murakami, Mari
	NRID 1000040548814 1000040548814 researchmap permalink 0425Kayama_Hisako 0425Kayama_Hisako Scopus Author ID 24390899100 24390899100 CreatorName Kayama, Hisako
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 CreatorName Okuzaki, Daisuke
	CreatorName Ikeda, Atsuyo
	NRID 1000000781709 1000000781709 researchmap permalink 00781709 00781709 Scopus Author ID 57193691322 57193691322 CreatorName Sekido, Yuki
	NRID 1000080749747 1000080749747 researchmap permalink tsuyoshi_hata tsuyoshi_hata Scopus Author ID 57189996374 57189996374 CreatorName Hata, Tsuyoshi
	NRID 1000060621034 1000060621034 ORCID 0000-0001-5535-3514 0000-0001-5535-3514 researchmap permalink hamabe_atsushi hamabe_atsushi CreatorName Hamabe, Atsushi
	CreatorName Takahashi, Hidekazu
	NRID 1000020528624 1000020528624 researchmap permalink nor nor Scopus Author ID 9242781300 9242781300 CreatorName Miyoshi, Norikatsu
	NRID 1000010528483 1000010528483 ORCID 0000-0001-6285-5619 0000-0001-6285-5619 researchmap permalink mamoruuemura mamoruuemura Scopus Author ID 36796497400 36796497400 CreatorName Uemura, Mamoru
	NRID 1000080319863 1000080319863 CreatorName Ikeuchi, Hiroki
	NRID 1000020309446 1000020309446 ORCID 0000-0002-1778-6332 0000-0002-1778-6332 researchmap permalink read0118278 read0118278 Scopus Author ID 7404335442 7404335442 CreatorName Takeda, Kiyoshi
	CreatorName Mizushima, Tsunekazu
	NRID 1000020291445 1000020291445 researchmap permalink ydoki3251 ydoki3251 Scopus Author ID 7006390687 7006390687 CreatorName Doki, Yuichiro
	NRID 1000090542118 1000090542118 researchmap permalink abcdabcdabcd abcdabcdabcd Scopus Author ID 7101627772 7101627772 CreatorName Eguchi, Hidetoshi
Subject	Crohn's disease
	Mesenteric fat
	Fibrogenesis
	Group 1 Innate lymphoid cell
Description	The version of record of this article, first published in Radiological Physics and Technology, is available online at Publisher’s website: https://doi.org/10.1007/s00535-025-02243-x.
Abstract	Background: Creeping fat is a characteristic of Crohn's disease and impacts the disease course. We evaluated creeping fat formation, focusing on innate lymphoid cell-mediated fibrogenesis and its clinical significance. Methods: Patients with inflammatory lesions in the ileum (the most commonly affected area), who underwent surgical resection at Osaka University or Hyogo Medical University (n = 34), were included. The ileum and mesentery were obtained from three sites: the control, non-creeping fat part, and creeping fat part. The distribution and properties of the innate lymphoid cells were analyzed by cell isolation. Furthermore, the correlation between macrophages and their effects on adipose tissue and clinical course were also investigated in a prospective cohort study. Results: Group 1 innate lymphoid cells in creeping fat were increased, correlating with inflammatory macrophages in the mesentery and showing higher interferon-γ expression. Co-culture experiment involving stromal vascular fraction from the control mesentery and Group 1 innate lymphoid cells from creeping fat revealed increased mRNA expression of fibrosis-related genes and inflammatory markers of macrophages, although these changes were nullified by interferon-γ-neutralizing antibody. Next, we examined the clinical importance of Group 1 innate lymphoid cells and identified their high frequency in creeping fat as a risk factor for early recurrence (P = 0.008, odds ratio: 1.19). Furthermore, the higher Group 1 innate lymphoid cell frequency group (≥ 80%) had shorter relapse-free survival (P = 0.03). Conclusions: Group 1 innate lymphoid cells and inflammatory macrophages contribute to creeping fat formation via interferon-γ secretion, affecting post-surgery intestinal outcomes.
Publisher	Springer
Source Title	Journal of Gastroenterology
Date of Issued	2025-03-29
Language	English
Handle URL	https://hdl.handle.net/11094/101112
PISSN	09441174
eISSN	14355922
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1007/s00535-025-02243-x
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Gastroenterology. 2025
DC.title	Group 1 innate lymphoid cells and inflammatory macrophages exacerbate fibrosis in creeping fat through IFN-γ secretion
DC.creator	Mori, Ryota
	Ogino, Takayuki
	Murakami, Mari
	Kayama, Hisako
	Okuzaki, Daisuke
	Ikeda, Atsuyo
	Sekido, Yuki
	Hata, Tsuyoshi
	Hamabe, Atsushi
	Takahashi, Hidekazu
	Miyoshi, Norikatsu
	Uemura, Mamoru
	Ikeuchi, Hiroki
	Takeda, Kiyoshi
	Mizushima, Tsunekazu
	Doki, Yuichiro
	Eguchi, Hidetoshi
DC.publisher	Springer
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-03-29
DC.identifier	https://doi.org/10.1007/s00535-025-02243-x
DC.subject	Crohn's disease
	Mesenteric fat
	Fibrogenesis
	Group 1 Innate lymphoid cell
DC.description	The version of record of this article, first published in Radiological Physics and Technology, is available online at Publisher’s website: https://doi.org/10.1007/s00535-025-02243-x.
DCTERMS.abstract	Background: Creeping fat is a characteristic of Crohn's disease and impacts the disease course. We evaluated creeping fat formation, focusing on innate lymphoid cell-mediated fibrogenesis and its clinical significance. Methods: Patients with inflammatory lesions in the ileum (the most commonly affected area), who underwent surgical resection at Osaka University or Hyogo Medical University (n = 34), were included. The ileum and mesentery were obtained from three sites: the control, non-creeping fat part, and creeping fat part. The distribution and properties of the innate lymphoid cells were analyzed by cell isolation. Furthermore, the correlation between macrophages and their effects on adipose tissue and clinical course were also investigated in a prospective cohort study. Results: Group 1 innate lymphoid cells in creeping fat were increased, correlating with inflammatory macrophages in the mesentery and showing higher interferon-γ expression. Co-culture experiment involving stromal vascular fraction from the control mesentery and Group 1 innate lymphoid cells from creeping fat revealed increased mRNA expression of fibrosis-related genes and inflammatory markers of macrophages, although these changes were nullified by interferon-γ-neutralizing antibody. Next, we examined the clinical importance of Group 1 innate lymphoid cells and identified their high frequency in creeping fat as a risk factor for early recurrence (P = 0.008, odds ratio: 1.19). Furthermore, the higher Group 1 innate lymphoid cell frequency group (≥ 80%) had shorter relapse-free survival (P = 0.03). Conclusions: Group 1 innate lymphoid cells and inflammatory macrophages contribute to creeping fat formation via interferon-γ secretion, affecting post-surgery intestinal outcomes.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	101112
citation_title	Group 1 innate lymphoid cells and inflammatory macrophages exacerbate fibrosis in creeping fat through IFN-γ secretion
citation_author	Mori, Ryota
	Ogino, Takayuki
	Murakami, Mari
	Kayama, Hisako
	Okuzaki, Daisuke
	Ikeda, Atsuyo
	Sekido, Yuki
	Hata, Tsuyoshi
	Hamabe, Atsushi
	Takahashi, Hidekazu
	Miyoshi, Norikatsu
	Uemura, Mamoru
	Ikeuchi, Hiroki
	Takeda, Kiyoshi
	Mizushima, Tsunekazu
	Doki, Yuichiro
	Eguchi, Hidetoshi
citation_publisher	Springer
citation_language	English
citation_date	2025-03-29
citation_journal_title	Journal of Gastroenterology
citation_doi	https://doi.org/10.1007/s00535-025-02243-x
citation_public_url	https://hdl.handle.net/11094/101112

Group 1 innate lymphoid cells and inflammatory macrophages exacerbate fibrosis in creeping fat through IFN-γ secretion

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