Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia
| Autor: | Edward Chung Yern Wang, Tomasz J. Slebioda, Vadim Y. Taraban, Aymen Al-Shamkhani, Sarah L. Buchan, Neil Smyth, Sonya James, Jane E. Willoughby, Gareth J. Thomas, Bhavwanti Sheth |
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| Rok vydání: | 2011 |
| Předmět: |
Tumor Necrosis Factor Ligand Superfamily Member 15
Regulatory T cell Immunology Mice Transgenic Biology Lymphocyte Activation T-Lymphocytes Regulatory Article Mice Intestinal mucosa medicine Animals Immunology and Allergy Intestinal Mucosa Receptors Tumor Necrosis Factor Member 25 Hyperplasia Interleukin-13 Interleukin-17 Interleukin medicine.disease Mice Inbred C57BL medicine.anatomical_structure Gene Expression Regulation Interleukin 13 Cancer research Tumor necrosis factor alpha Goblet Cells Interleukin 17 Death receptor 3 |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/mi.2010.70 |
| Popis: | The tumor necrosis factor (TNF) superfamily protein TNF-like 1A (TL1A) is the ligand for death receptor 3 (DR3). TL1A is induced on activated dendritic cells (DCs) and its expression has been linked to human inflammatory bowel disease. To address how TL1A might influence intestinal inflammation, we generated transgenic mice that constitutively express TL1A on DCs. TL1A transgenic mice developed striking goblet cell hyperplasia in the ileum that was associated with elevated interleukin (IL)-13 levels in the small intestine. IL-13- and IL-17-producing small intestinal lamina propria T cells were increased in TL1A transgenic mice. TL1A also enhanced regulatory T (Treg) cell turnover in vivo and directly stimulated Treg cell proliferation in vitro. The presence of TL1A attenuated the ability of Treg cells to suppress conventional T cells, an effect that required DR3 signaling in either conventional T cells or Treg cells. Our findings identify mechanisms by which chronic DR3 signaling could promote pathogenesis in inflammatory bowel disease. |
| Databáze: | OpenAIRE |
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