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Keep calm: the intestinal barrier at the interface of peace and war

Type of publication Peer-reviewed
Publikationsform Review article (peer-reviewed)
Author Thoo Lester, Noti Mario, Krebs Philippe,
Project mRNA splicing and epithelial integrity
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Review article (peer-reviewed)

Journal Cell Death & Disease
Page(s) 1/849 - 13
Title of proceedings Cell Death & Disease
DOI 10.1038/s41419-019-2086-z

Open Access

URL https://www.nature.com/articles/s41419-019-2086-z.pdf
Type of Open Access Publisher (Gold Open Access)

Abstract

Epithelial barriers have to constantly cope with both harmless and harmful stimuli. The epithelial barrier thereforeserves as a dynamic and not static wall to safeguard its proper physiological function while ensuring protection. This isachieved through multiple defence mechanisms involving various cell types - epithelial and non-epithelial - that workin an integrated manner to build protective barriers at mucosal sites. Damage may nevertheless occur, due topathogens, physical insults or dysregulated immune responses, which trigger a physiologic acute or a pathologicchronic inflammatory cascade. Inflammation is often viewed as a pathological condition, particularly due to theincreasing prevalence of chronic inflammatory (intestinal) diseases. However, inflammation is also necessary for woundhealing. The aetiology of chronic inflammatory diseases is incompletely understood and identification of theunderlying mechanisms would reveal additional therapeutic approaches. Resolution is an active host response to endongoing inflammation but its relevance is under-appreciated. Currently, most therapies aim at dampeninginflammation at damaged mucosal sites, yet these approaches do not efficiently shut down the inflammation processnor repair the epithelial barrier. Therefore, future treatment strategies should also promote the resolution phase. Yet,the task of repairing the barrier can be an arduous endeavour considering its multiple integrated layers of defence -which is advantageous for damage prevention but becomes challenging to repair at multiple levels. In this review,using the intestines as a model epithelial organ and barrier paradigm, we describe the consequences of chronicinflammation and highlight the importance of the mucosae to engage resolving processes to restore epithelial barrierintegrity and function. We further discuss the contribution of pre-mRNA alternative splicing to barrier integrity andintestinal homeostasis. Following discussions on current open questions and challenges, we propose a model inwhich resolution of inflammation represents a key mechanism for the restoration of epithelial integrity and function.
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