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Critical role of the disintegrin metalloprotease ADAM-like Decysin-1 (ADAMDEC1) for intestinal immunity and inflammation

O'Shea, NR; Chew, TS; Dunne, J; Marnane, R; Nedjat-Shokouhi, B; Smith, PJ; Bloom, SL; ... Segal, AW; + view all (2016) Critical role of the disintegrin metalloprotease ADAM-like Decysin-1 (ADAMDEC1) for intestinal immunity and inflammation. Journal of Crohn's and Colitis , 10 (12) pp. 1417-1427. 10.1093/ecco-jcc/jjw111. Green open access

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Abstract

BACKGROUND AND AIMS: ADAM (A Disintegrin And Metalloproteinase) is a family of peptidase proteins, which have diverse roles in tissue homeostasis and immunity. Here, we study ADAM-like Decysin-1 (ADAMDEC1) a unique member of the ADAM family. ADAMDEC1 expression is restricted to the macrophage/dendritic cell populations of the gastrointestinal tract and secondary lymphoid tissue. The biological function of ADAMDEC1 is unknown but it has been hypothesised to play a role in immunity. The identification of reduced ADAMDEC1 expression in Crohn's disease patients has provided evidence of a potential role in bowel inflammation. METHODS: Adamdec1(-/-) mice were exposed to dextran sodium sulphate or infected orally with Citrobacter rodentium or Salmonella typhimurium The clinical response was monitored. RESULTS: The loss of Adamdec1 rendered mice more susceptible to the induction of bacterial and chemical induced colitis, as evidenced by increased neutrophil infiltration, greater IL-6 and IL-1β secretion, more weight loss and increased mortality. In the absence of Adamdec1, greater numbers of Citrobacter rodentium were found in the spleen, suggestive of a breakdown in mucosal immunity which resulted in bacteraemia. CONCLUSION: In summary, Adamdec1 protects the bowel from chemical and bacterial insults, failure of which may predispose to Crohn's disease.

Type: Article
Title: Critical role of the disintegrin metalloprotease ADAM-like Decysin-1 (ADAMDEC1) for intestinal immunity and inflammation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/ecco-jcc/jjw111
Publisher version: http://dx.doi.org/10.1093/ecco-jcc/jjw111
Language: English
Additional information: Copyright © European Crohn’s and Colitis Organisation 2016. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Citrobacter rodentium, Colitis, DSS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute
URI: https://discovery.ucl.ac.uk/id/eprint/1496813
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