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Human intestinal myofibroblasts deposited collagen VI enhances adhesiveness for T cells - A novel mechanism for maintenance of intestinal inflammation.
Lin, Si-Nan; Musso, Alessandro; Wang, Jie; Mukherjee, Pranab K; West, Gail A; Mao, Ren; Lyu, Ruishen; Li, Jiannan; Zhao, Shuai; Elias, Michael; Haberman, Yael; Denson, Lee A; Kugathasan, Subra; Chen, Min-Hu; Czarnecki, Doug; Dejanovic, Dina; Le, Hongnga T; Chandra, Jyotsna; Lipman, Jeremy; Steele, Scott R; Nguyen, Quang Tam; Fiocchi, Claudio; Rieder, Florian.
Affiliation
  • Lin SN; Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Musso A; Division of Gastroenterology, Città della Salute e della Scienza di Torino, Molinette Hospital, Turin, Italy.
  • Wang J; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan, China.
  • Mukherjee PK; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • West GA; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Mao R; Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Lyu R; Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
  • Li J; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Zhao S; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Elias M; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Haberman Y; Sheba Medical Center, Tel Hashomer, Affiliated with the Tel Aviv University, Tel Aviv, Israel; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Denson LA; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Kugathasan S; Department of Pediatrics, Emory University, Atlanta, GA, USA.
  • Chen MH; Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • Czarnecki D; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Dejanovic D; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Le HT; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Chandra J; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Lipman J; Department of Surgery, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Steele SR; Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Nguyen QT; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Fiocchi C; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue - NC22, Cleveland, OH, USA.
  • Rieder F; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue - NC22, Cleveland, OH, USA. Electronic address: riederf@ccf.org.
Matrix Biol ; 113: 1-21, 2022 11.
Article in En | MEDLINE | ID: mdl-36108990
ABSTRACT

OBJECTIVE:

Inflammatory bowel diseases (IBD) cause chronic intestinal damage and extracellular matrix (ECM) remodeling. The ECM may play an active role in inflammation by modulating immune cell functions, including cell adhesion, but this hypothesis has not been tested in IBD.

DESIGN:

Primary human intestinal myofibroblast (HIMF)-derived ECM from IBD and controls, 3D decellularized colon or ECM molecule-coated scaffolds were tested for their adhesiveness for T cells. Matrisome was analysed via proteomics. Functional integrin blockade was used to investigate the underlying mechanism. Analysis of the pediatric Crohn's disease (CD) RISK inception cohort was used to explore an altered ECM gene expression as a potential predictor for a future complicated disease course.

RESULTS:

HIMF-derived ECM and 3D decellularized colonic ECM from IBD bound more T cells compared to control. Control HIMFs exposed to the pro-inflammatory cytokines Iinterleukin-1ß (IL-1ß) and tumor necrosis factor (TNF) increased, and to transforming growth factor-ß1 (TGF-ß1) decreased ECM adhesiveness to T cells. Matrisome analysis of the HIMF-derived ECM revealed collagen VI as a major culprit for differences in T cell adhesion. Collagen VI knockdown in HIMF reduced adhesion T cell as did the blockage of integrin αvß1. Elevated gene expression of collagen VI in biopsies of pediatric CD patients was linked to risk for future stricturing disease.

CONCLUSION:

HIMF-derived ECM in IBD binds a remarkably enhanced number of T cells, which is dependent on Collagen VI and integrin αvß1. Collagen VI expression is a risk factor for a future complicated CD course. Blocking immune cells retention may represent a novel approach to treatment in IBD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Inflammatory Bowel Diseases / Myofibroblasts Type of study: Prognostic_studies / Risk_factors_studies Limits: Child / Humans Language: En Journal: Matrix Biol Journal subject: BIOLOGIA MOLECULAR / BIOQUIMICA Year: 2022 Document type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Inflammatory Bowel Diseases / Myofibroblasts Type of study: Prognostic_studies / Risk_factors_studies Limits: Child / Humans Language: En Journal: Matrix Biol Journal subject: BIOLOGIA MOLECULAR / BIOQUIMICA Year: 2022 Document type: Article Affiliation country: United States