Smad7 as a positive regulator of intestinal inflammatory diseases
In physiological conditions, the human gut contains more immune cells than the rest of the body, but no overt tissue damage occurs, because several regulatory mechanisms control the activity of such cells thus preventing excessive and detrimental responses. One such mechanism relies on the action of...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Current Research in Immunology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S259025552300001X |
| _version_ | 1797422485259419648 |
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| author | Giovanni Monteleone Federica Laudisi Carmine Stolfi |
| author_facet | Giovanni Monteleone Federica Laudisi Carmine Stolfi |
| author_sort | Giovanni Monteleone |
| collection | DOAJ |
| description | In physiological conditions, the human gut contains more immune cells than the rest of the body, but no overt tissue damage occurs, because several regulatory mechanisms control the activity of such cells thus preventing excessive and detrimental responses. One such mechanism relies on the action of transforming growth factor (TGF)-β1, a cytokine that targets both epithelial cells and many immune cell types. Loss of TGF-β1 function leads to intestinal pathology in both mice and humans. For instance, disruption of TGF-β1 signaling characterizes the destructive immune-inflammatory response in patients with Crohn’s disease and patients with ulcerative colitis, the major human inflammatory bowel disease (IBD) entities. In these pathologies, the defective TGF-β1-mediated anti-inflammatory response is associated with elevated intestinal levels of Smad7, an antagonist of TGF-β1 signaling. Consistently, knockdown of Smad7 restores TGF-β1 function thereby attenuating intestinal inflammation in patients with IBD as well as in mice with IBD-like colitis. Up-regulation of Smad7 and reduced TGF-β1 signaling occurs also in necrotizing enterocolitis, environmental enteropathy, refractory celiac disease, and cytomegalovirus-induced colitis. In this article, we review the available data supporting the pathogenic role of Smad7 in the gastrointestinal tract and discuss whether and how targeting Smad7 can help attenuate detrimental immuno-inflammatory responses in the gut. |
| first_indexed | 2024-03-09T07:33:59Z |
| format | Article |
| id | doaj.art-252719d52e8e4030950ece29e20aba8c |
| institution | Directory Open Access Journal |
| issn | 2590-2555 |
| language | English |
| last_indexed | 2024-03-09T07:33:59Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Immunology |
| spelling | doaj.art-252719d52e8e4030950ece29e20aba8c2023-12-03T05:42:47ZengElsevierCurrent Research in Immunology2590-25552023-01-014100055Smad7 as a positive regulator of intestinal inflammatory diseasesGiovanni Monteleone0Federica Laudisi1Carmine Stolfi2Corresponding author. Dipartimento di Medicina dei Sistemi, Università di Roma “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy.; Department of Systems Medicine, University of Rome “Tor Vergata”, Director of Gastroenterology Unit, Department of Medical Science, Policlinico Universitario Tor Vergata, Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, Director of Gastroenterology Unit, Department of Medical Science, Policlinico Universitario Tor Vergata, Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, Director of Gastroenterology Unit, Department of Medical Science, Policlinico Universitario Tor Vergata, Rome, ItalyIn physiological conditions, the human gut contains more immune cells than the rest of the body, but no overt tissue damage occurs, because several regulatory mechanisms control the activity of such cells thus preventing excessive and detrimental responses. One such mechanism relies on the action of transforming growth factor (TGF)-β1, a cytokine that targets both epithelial cells and many immune cell types. Loss of TGF-β1 function leads to intestinal pathology in both mice and humans. For instance, disruption of TGF-β1 signaling characterizes the destructive immune-inflammatory response in patients with Crohn’s disease and patients with ulcerative colitis, the major human inflammatory bowel disease (IBD) entities. In these pathologies, the defective TGF-β1-mediated anti-inflammatory response is associated with elevated intestinal levels of Smad7, an antagonist of TGF-β1 signaling. Consistently, knockdown of Smad7 restores TGF-β1 function thereby attenuating intestinal inflammation in patients with IBD as well as in mice with IBD-like colitis. Up-regulation of Smad7 and reduced TGF-β1 signaling occurs also in necrotizing enterocolitis, environmental enteropathy, refractory celiac disease, and cytomegalovirus-induced colitis. In this article, we review the available data supporting the pathogenic role of Smad7 in the gastrointestinal tract and discuss whether and how targeting Smad7 can help attenuate detrimental immuno-inflammatory responses in the gut.http://www.sciencedirect.com/science/article/pii/S259025552300001XCrohn’s diseaseUlcerative colitisInflammatory bowel diseasesTGF-beta |
| spellingShingle | Giovanni Monteleone Federica Laudisi Carmine Stolfi Smad7 as a positive regulator of intestinal inflammatory diseases Current Research in Immunology Crohn’s disease Ulcerative colitis Inflammatory bowel diseases TGF-beta |
| title | Smad7 as a positive regulator of intestinal inflammatory diseases |
| title_full | Smad7 as a positive regulator of intestinal inflammatory diseases |
| title_fullStr | Smad7 as a positive regulator of intestinal inflammatory diseases |
| title_full_unstemmed | Smad7 as a positive regulator of intestinal inflammatory diseases |
| title_short | Smad7 as a positive regulator of intestinal inflammatory diseases |
| title_sort | smad7 as a positive regulator of intestinal inflammatory diseases |
| topic | Crohn’s disease Ulcerative colitis Inflammatory bowel diseases TGF-beta |
| url | http://www.sciencedirect.com/science/article/pii/S259025552300001X |
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