The Role of Citrullination in Inflammatory Bowel Disease: A Neglected Player in Triggering Inflammation and Fibrosis?

Abstract:

:Citrullination is a posttranslational modification of proteins mediated by a specific family of enzymes called peptidylarginine deiminases (PAD). Dysregulation of these enzymes is involved in the etiology of various diseases, from cancer to autoimmune disorders. In inflammatory bowel disease (IBD), data for a role of citrullination in the disease process are starting to accumulate at different experimental levels including gene expression analyses, RNA, and protein quantifications. Most data have been generated in ulcerative colitis, but data in Crohn disease are lacking so far. In addition, the citrullination of histones is the fundamental process promoting inflammation through the formation of neutrophil extracellular traps (NETs). Interestingly, NETs have also been shown to activate fibroblasts into myofibroblasts in fibrotic interstitial lung disease. Therefore, citrullination merits more thorough study in the bowel to determine its role in driving disease complications such as fibrosis. In this review we describe the process of citrullination and the different players in this pathway, the role of citrullination in autoimmunity with a special focus on IBD, the emerging role for citrullination and NETs in triggering fibrosis, and, finally, how this process could be therapeutically targeted.

journal_name

Inflamm Bowel Dis

authors

Dragoni G,De Hertogh G,Vermeire S

doi

10.1093/ibd/izaa095

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

134-144

issue

1

eissn

1078-0998

issn

1536-4844

pii

5840491

journal_volume

27

pub_type

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