期刊
MUCOSAL IMMUNOLOGY
卷 14, 期 3, 页码 667-678出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/s41385-021-00375-w
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资金
- French Ministry of Research and Technology
- National Agency for Research [ANR JCJC-11JSV1 001 01, ANR-12-BSV1-0030-01]
- European IOF Marie Curie Action Project [FP7-627487]
- European Research Council [ERC- PIPE-310973]
- delegation regionale a la recherche clinique des hopitaux de Toulouse, through the AOL-MICILIP project
- CCFC grant
- Programme des Investissements d'Avenir ANINFIMIP [ANR-11EQPX-0003]
- Agence Nationale de la Recherche (ANR) [ANR-12-BSV1-0030] Funding Source: Agence Nationale de la Recherche (ANR)
Imbalance between proteases and their inhibitors is crucial in the development of Inflammatory Bowel Diseases (IBD). This study identifies a previously unrevealed production of elastase 2A (ELA2A) by colonic epithelial cells in IBD patients, leading to inflammation and loss of barrier function. Targeting ELA2A hyperactivity could be a potential treatment for IBD.
Imbalance between proteases and their inhibitors plays a crucial role in the development of Inflammatory Bowel Diseases (IBD). Increased elastolytic activity is observed in the colon of patients suffering from IBD. Here, we aimed at identifying the players involved in elastolytic hyperactivity associated with IBD and their contribution to the disease. We revealed that epithelial cells are a major source of elastolytic activity in healthy human colonic tissues and this activity is greatly increased in IBD patients, both in diseased and distant sites of inflammation. This study identified a previously unrevealed production of elastase 2A (ELA2A) by colonic epithelial cells, which was enhanced in IBD patients. We demonstrated that ELA2A hyperactivity is sufficient to lead to a leaky epithelial barrier. Epithelial ELA2A hyperactivity also modified the cytokine gene expression profile with an increase of pro-inflammatory cytokine transcripts, while reducing the expression of pro-resolving and repair factor genes. ELA2A thus appears as a novel actor produced by intestinal epithelial cells, which can drive inflammation and loss of barrier function, two essentials pathophysiological hallmarks of IBD. Targeting ELA2A hyperactivity should thus be considered as a potential target for IBD treatment.
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