Show simple item record

dc.contributor.authorFALLON, PADRAICen
dc.date.accessioned2015-12-11T12:04:42Z
dc.date.available2015-12-11T12:04:42Z
dc.date.issued2014en
dc.date.submitted2014en
dc.identifier.citationSchiering C, Krausgruber T, Chomka A, Fröhlich A, Adelmann K, Wohlfert EA, Pott J, Griseri T, Bollrath J, Hegazy AN, Harrison OJ, Owens BM, Löhning M, Belkaid Y, Fallon PG, Powrie F., The alarmin IL-33 promotes regulatory T-cell function in the intestine., Nature, Jul 16, 2014en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/75277
dc.descriptionPUBLISHEDen
dc.description.abstractFOXP3(+) regulatory T cells (Treg cells) are abundant in the intestine, where they prevent dysregulated inflammatory responses to self and environmental stimuli. It is now appreciated that Treg cells acquire tissue-specific adaptations that facilitate their survival and function; however, key host factors controlling the Treg response in the intestine are poorly understood. The interleukin (IL)-1 family member IL-33 is constitutively expressed in epithelial cells at barrier sites, where it functions as an endogenous danger signal, or alarmin, in response to tissue damage. Recent studies in humans have described high levels of IL-33 in inflamed lesions of inflammatory bowel disease patients, suggesting a role for this cytokine in disease pathogenesis. In the intestine, both protective and pathological roles for IL-33 have been described in murine models of acute colitis, but its contribution to chronic inflammation remains ill defined. Here we show in mice that the IL-33 receptor ST2 is preferentially expressed on colonic Treg cells, where it promotes Treg function and adaptation to the inflammatory environment. IL-33 signalling in T cells stimulates Treg responses in several ways. First, it enhances transforming growth factor (TGF)-β1-mediated differentiation of Treg cells and, second, it provides a necessary signal for Treg-cell accumulation and maintenance in inflamed tissues. Strikingly, IL-23, a key pro-inflammatory cytokine in the pathogenesis of inflammatory bowel disease, restrained Treg responses through inhibition of IL-33 responsiveness. These results demonstrate a hitherto unrecognized link between an endogenous mediator of tissue damage and a major anti-inflammatory pathway, and suggest that the balance between IL-33 and IL-23 may be a key controller of intestinal immune responses.en
dc.language.isoenen
dc.relation.ispartofseriesNatureen
dc.relation.ispartofseriesJul 16en
dc.rightsYen
dc.subjectT-cellsen
dc.titleThe alarmin IL-33 promotes regulatory T-cell function in the intestine.en
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/pfallonen
dc.identifier.rssinternalid96670en
dc.identifier.doihttp://dx.doi.org/10.1038/nature13577en
dc.rights.ecaccessrightsopenAccess
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.subject.TCDTagBiomedical sciencesen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record