Dysfunctional intestinal microvascular endothelial cells: Insights and therapeutic implications in gastrointestinal inflammation

Dysfunctional intestinal microvascular endothelial cells: Insights and therapeutic implications in gastrointestinal inflammation

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DOI 10.1097/IN9.0000000000000043
刊名
IJ
年,卷(期) 2024, 6(2)
作者
作者单位

[Park, Ji Seok;
Cresci, Gail A. M.] Cleveland Clin, Digest Dis Inst, Dept Gastroenterol Hepatol & Nutr, Cleveland, OH 44106 USA;
[Park, Ji Seok;
Cresci, Gail A. M.] Cleveland Clin, Lerner Res Inst, Dept Inflammat & Immun, Cleveland, OH 44106 USA;
[Cresci,

摘要
The intestinal microvascular endothelium plays a crucial role in orchestrating host responses to inflammation within the gastrointestinal tract. This review delves into the unique aspects of intestinal microvascular endothelial cells, distinct from those of larger vessels, in mediating leukocyte recruitment, maintaining barrier integrity, and regulating angiogenesis during inflammation. Specifically, their role in the pathogenesis of inflammatory bowel diseases, where dysregulated endothelial functions contribute to the disease progression, is reviewed. Furthermore, this review discusses the isolation technique for these cells and commonly used adhesion molecules for in vitro and in vivo experiments. In addition, we reviewed the development and therapeutic implications of a biologic agent targeting the interaction between alpha 4 beta 7 integrin on T lymphocytes and mucosal addressin cellular adhesion molecule-1 on gut endothelium. Notably, vedolizumab, a humanized monoclonal antibody against alpha 4 beta 7 integrin, has shown promising outcomes in inflammatory bowel diseases and other gastrointestinal inflammatory conditions, including chronic pouchitis, immune checkpoint inhibitor-induced colitis, and acute cellular rejection post-intestinal transplantation.
Abstract
The intestinal microvascular endothelium plays a crucial role in orchestrating host responses to inflammation within the gastrointestinal tract. This review delves into the unique aspects of intestinal microvascular endothelial cells, distinct from those of larger vessels, in mediating leukocyte recruitment, maintaining barrier integrity, and regulating angiogenesis during inflammation. Specifically, their role in the pathogenesis of inflammatory bowel diseases, where dysregulated endothelial functions contribute to the disease progression, is reviewed. Furthermore, this review discusses the isolation technique for these cells and commonly used adhesion molecules for in vitro and in vivo experiments. In addition, we reviewed the development and therapeutic implications of a biologic agent targeting the interaction between alpha 4 beta 7 integrin on T lymphocytes and mucosal addressin cellular adhesion molecule-1 on gut endothelium. Notably, vedolizumab, a humanized monoclonal antibody against alpha 4 beta 7 integrin, has shown promising outcomes in inflammatory bowel diseases and other gastrointestinal inflammatory conditions, including chronic pouchitis, immune checkpoint inhibitor-induced colitis, and acute cellular rejection post-intestinal transplantation.
关键词
intestinal microvascular endothelial cells; leukocyte homing; inflammatory bowel disease; mucosal addressin cellular adhesion molecule-1; alpha(4)beta(7) integrin; vedolizumab
KeyWord
intestinal microvascular endothelial cells; leukocyte homing; inflammatory bowel disease; mucosal addressin cellular adhesion molecule-1; alpha(4)beta(7) integrin; vedolizumab
基金项目
页码 1-5
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Park, Ji Seok; Cresci, Gail A. M.. Dysfunctional intestinal microvascular endothelial cells: Insights and therapeutic implications in gastrointestinal inflammation [J]. Immunometabolism. 2024; 6; (2). 1 - 5.

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