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dc.contributor.authorBarry, R
dc.contributor.authorRuano-Gallego, D
dc.contributor.authorRadhakrishnan, ST
dc.contributor.authorLovell, S
dc.contributor.authorYu, L
dc.contributor.authorKotik, O
dc.contributor.authorGlegola-Madejska, I
dc.contributor.authorTate, EW
dc.contributor.authorChoudhary, JS
dc.contributor.authorWilliams, HRT
dc.contributor.authorFrankel, G
dc.date.accessioned2020-05-27T14:20:50Z
dc.date.issued2020-03
dc.identifier.citationMucosal immunology, 2020, 13 (2), pp. 322 - 333
dc.identifier.issn1933-0219
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3639
dc.identifier.eissn1935-3456
dc.identifier.doi10.1038/s41385-019-0235-4
dc.description.abstractGiven the global burden of diarrheal diseases on healthcare it is surprising how little is known about the drivers of disease severity. Colitis caused by infection and inflammatory bowel disease (IBD) is characterised by neutrophil infiltration into the intestinal mucosa and yet our understanding of neutrophil responses during colitis is incomplete. Using infectious (Citrobacter rodentium) and chemical (dextran sulphate sodium; DSS) murine colitis models, as well as human IBD samples, we find that faecal neutrophil elastase (NE) activity reflects disease severity. During C. rodentium infection intestinal epithelial cells secrete the serine protease inhibitor SerpinA3N to inhibit and mitigate tissue damage caused by extracellular NE. Mice suffering from severe infection produce insufficient SerpinA3N to control excessive NE activity. This activity contributes to colitis severity as infection of these mice with a recombinant C. rodentium strain producing and secreting SerpinA3N reduces tissue damage. Thus, uncontrolled luminal NE activity is involved in severe colitis. Taken together, our findings suggest that NE activity could be a useful faecal biomarker for assessing disease severity as well as therapeutic target for both infectious and chronic inflammatory colitis.
dc.formatPrint-Electronic
dc.format.extent322 - 333
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectNeutrophils
dc.subjectFeces
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectCitrobacter rodentium
dc.subjectEnterobacteriaceae Infections
dc.subjectColitis
dc.subjectInflammatory Bowel Diseases
dc.subjectDisease Models, Animal
dc.subjectDisease Progression
dc.subjectLeukocyte Elastase
dc.subjectDextran Sulfate
dc.subjectAcute-Phase Proteins
dc.subjectSerpins
dc.subjectProtease Inhibitors
dc.subjectSeverity of Illness Index
dc.subjectBiomarkers
dc.titleFaecal neutrophil elastase-antiprotease balance reflects colitis severity.
dc.typeJournal Article
dcterms.dateAccepted2019-11-07
rioxxterms.versionofrecord10.1038/s41385-019-0235-4
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMucosal immunology
pubs.issue2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume13
pubs.embargo.termsNot known
dc.contributor.icrauthorChoudhary, Jyotien


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