Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis.
TL1A is a member of the TNF superfamily and its expression is increased in the mucosa of inflammatory bowel disease patients. Moreover, a subset of Crohn's disease (CD) patients with the risk TL1A haplotype is associated with elevated TL1A expression and a more severe disease course. To investi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3019214?pdf=render |
| _version_ | 1818957770568761344 |
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| author | David Q Shih Robert Barrett Xiaolan Zhang Nicole Yeager Hon Wai Koon Piangwarin Phaosawasdi Yahui Song Brian Ko Michelle H Wong Kathrin S Michelsen Gislaine Martins Charalabos Pothoulakis Stephan R Targan |
| author_facet | David Q Shih Robert Barrett Xiaolan Zhang Nicole Yeager Hon Wai Koon Piangwarin Phaosawasdi Yahui Song Brian Ko Michelle H Wong Kathrin S Michelsen Gislaine Martins Charalabos Pothoulakis Stephan R Targan |
| author_sort | David Q Shih |
| collection | DOAJ |
| description | TL1A is a member of the TNF superfamily and its expression is increased in the mucosa of inflammatory bowel disease patients. Moreover, a subset of Crohn's disease (CD) patients with the risk TL1A haplotype is associated with elevated TL1A expression and a more severe disease course. To investigate the in vivo role of elevated TL1A expression, we generated two transgenic (Tg) murine models with constitutive Tl1a expression in either lymphoid or myeloid cells. Compared to wildtype (WT) mice, constitutive expression of Tl1a in either lymphoid or myeloid cells showed mild patchy inflammation in the small intestine, which was more prominent in the ileum. In addition, mice with constitutive Tl1a expression exhibited enhanced intestinal and colonic fibrosis compared to WT littermates. The percentage of T cells expressing the gut homing chemokine receptors CCR9 and CCR10 was higher in the Tl1a Tg mice compared to WT littermates. Sustained expression of Tl1A in T cells also lead to increased Foxp3+ Treg cells. T cells or antigen presenting cells (APC) with constitutive expression of Tl1a were found to have a more activated phenotype and mucosal mononuclear cells exhibit enhanced Th1 cytokine activity. These results indicated an important role of TL1A in mucosal T cells and APC function and showed that up-regulation of TL1A expression can promote mucosal inflammation and gut fibrosis. |
| first_indexed | 2024-12-20T11:15:08Z |
| format | Article |
| id | doaj.art-9d4d782a89f445189668f80a41d5488f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T11:15:08Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9d4d782a89f445189668f80a41d5488f2022-12-21T19:42:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1609010.1371/journal.pone.0016090Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis.David Q ShihRobert BarrettXiaolan ZhangNicole YeagerHon Wai KoonPiangwarin PhaosawasdiYahui SongBrian KoMichelle H WongKathrin S MichelsenGislaine MartinsCharalabos PothoulakisStephan R TarganTL1A is a member of the TNF superfamily and its expression is increased in the mucosa of inflammatory bowel disease patients. Moreover, a subset of Crohn's disease (CD) patients with the risk TL1A haplotype is associated with elevated TL1A expression and a more severe disease course. To investigate the in vivo role of elevated TL1A expression, we generated two transgenic (Tg) murine models with constitutive Tl1a expression in either lymphoid or myeloid cells. Compared to wildtype (WT) mice, constitutive expression of Tl1a in either lymphoid or myeloid cells showed mild patchy inflammation in the small intestine, which was more prominent in the ileum. In addition, mice with constitutive Tl1a expression exhibited enhanced intestinal and colonic fibrosis compared to WT littermates. The percentage of T cells expressing the gut homing chemokine receptors CCR9 and CCR10 was higher in the Tl1a Tg mice compared to WT littermates. Sustained expression of Tl1A in T cells also lead to increased Foxp3+ Treg cells. T cells or antigen presenting cells (APC) with constitutive expression of Tl1a were found to have a more activated phenotype and mucosal mononuclear cells exhibit enhanced Th1 cytokine activity. These results indicated an important role of TL1A in mucosal T cells and APC function and showed that up-regulation of TL1A expression can promote mucosal inflammation and gut fibrosis.http://europepmc.org/articles/PMC3019214?pdf=render |
| spellingShingle | David Q Shih Robert Barrett Xiaolan Zhang Nicole Yeager Hon Wai Koon Piangwarin Phaosawasdi Yahui Song Brian Ko Michelle H Wong Kathrin S Michelsen Gislaine Martins Charalabos Pothoulakis Stephan R Targan Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis. PLoS ONE |
| title | Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis. |
| title_full | Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis. |
| title_fullStr | Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis. |
| title_full_unstemmed | Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis. |
| title_short | Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis. |
| title_sort | constitutive tl1a tnfsf15 expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis |
| url | http://europepmc.org/articles/PMC3019214?pdf=render |
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