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The alarmin IL-33 promotes regulatory T-cell function in the intestine.
- Source :
-
Nature [Nature] 2014 Sep 25; Vol. 513 (7519), pp. 564-568. Date of Electronic Publication: 2014 Jul 16. - Publication Year :
- 2014
-
Abstract
- FOXP3(+) 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.
- Subjects :
- Animals
Colitis immunology
Colitis pathology
Colon cytology
Colon immunology
Colon pathology
Disease Models, Animal
Female
Immunity, Mucosal
Inflammation immunology
Inflammation metabolism
Inflammation pathology
Interleukin-23 immunology
Interleukin-33
Interleukins antagonists & inhibitors
Interleukins metabolism
Intestines pathology
Male
Mice
Mice, Inbred C57BL
Receptors, Interleukin metabolism
Signal Transduction immunology
T-Lymphocytes, Regulatory cytology
Thymus Gland cytology
Transforming Growth Factor beta metabolism
Interleukins immunology
Intestines cytology
Intestines immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 513
- Issue :
- 7519
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 25043027
- Full Text :
- https://doi.org/10.1038/nature13577