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Creeping fat exhibits distinct Inflammation-specific adipogenic preadipocytes in Crohn's disease

Authors
 Nahee Hwang  ;  Dongwoo Kang  ;  Su-Jin Shin  ;  Bo Kyung Yoon  ;  Jaeyoung Chun  ;  Jae-Woo Kim  ;  Sungsoon Fang 
Citation
 FRONTIERS IN IMMUNOLOGY, Vol.14 : 1198905, 2023-12 
Journal Title
FRONTIERS IN IMMUNOLOGY
Issue Date
2023-12
MeSH
Adipogenesis ; Adipose Tissue / metabolism ; Crohn Disease* ; Cytokines / metabolism ; Fibrosis ; Humans ; Immunoglobulin G / metabolism ; Inflammation / metabolism ; Lymphedema*
Keywords
Crohn’s disease ; creeping fat ; fat fibrosis ; fibroblast ; inflammation ; inflammatory bowel disease ; pentraxin-3 ; preadipocytes
Abstract
Creeping fat (CrF) is an extraintestinal manifestation observed in patients with Crohn's disease (CD). It is characterized by the accumulation of mesenteric adipose tissue (MAT) that wraps around the intestinal wall. Although the role of CrF in CD is still debated, multiple studies have highlighted a correlation between CrF and inflammation, as well as fibrostenosais of the intestine, which contributes to the worsening of CD symptoms. However, the mechanism underlying the potential role of CrF in the development of Crohn's fibrosis remains an enigma. This study aimed to analyze CrF comprehensively using single-cell RNA sequencing analysis. The data was compared with transcriptomic data from adipose tissue in other disease conditions, such as ulcerative colitis, lymphedema, and obesity. Our analysis classified two lineages of preadipocyte (PAC) clusters responsible for adipogenesis and fibrosis in CrF. Committed PACs in CrF showed increased cytokine expression in response to bacterial stimuli, potentially worsening inflammation in patients with CD. We also observed an increase in fibrotic activity in PAC clusters in CrF. Co-analyzing the data from patients with lymphedema, we found that pro-fibrotic PACs featured upregulated pentraxin-3 expression, suggesting a potential target for the treatment of fibrosis in CrF. Furthermore, PACs in CrF exhibited a distinct increase in cell-to-cell communication via cytokines related to inflammation and fibrosis, such as CCL, LIGHT, PDGF, MIF, and SEMA3. Interestingly, these interactions also increased in PACs of the lymphedema, whereas the increased MIF signal of PACs was found to be a distinct characteristic of CrF. In immune cell clusters in CrF, we observed high immune activity of pro-inflammatory macrophages, antigen-presenting macrophages, B cells, and IgG+ plasma cells. Finally, we have demonstrated elevated IgG+ plasma cell infiltration and increased pentraxin-3 protein levels in the fibrotic regions of CrF in CD patients when compared to MAT from both UC patients and healthy individuals. These findings provide new insights into the transcriptomic features related to the inflammation of cells in CrF and suggest potential targets for attenuating fibrosis in CD.
Files in This Item:
T202306718.pdf Download
DOI
10.3389/fimmu.2023.1198905
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Shin, Su Jin(신수진) ORCID logo https://orcid.org/0000-0001-9114-8438
Yoon, Bo Kyung(윤보경)
Chun, Jaeyoung(천재영) ORCID logo https://orcid.org/0000-0002-4212-0380
Fang, Sungsoon(황성순) ORCID logo https://orcid.org/0000-0003-0201-5567
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/197342
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