Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia
Authors: Taraban, V.Y., Slebioda, T.J., Willoughby, J.E., Buchan, S.L., James, S., Sheth, B., Smyth, N.R., Thomas, G.J., Wang, E.C.Y. and Al-Shamkhani, A.
Journal: Mucosal Immunology
Volume: 4
Issue: 2
Pages: 186-196
ISSN: 1933-0219
DOI: 10.1038/mi.2010.70
Abstract: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. © 2011 Society for Mucosal Immunology.
Source: Scopus
Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia.
Authors: Taraban, V.Y., Slebioda, T.J., Willoughby, J.E., Buchan, S.L., James, S., Sheth, B., Smyth, N.R., Thomas, G.J., Wang, E.C.Y. and Al-Shamkhani, A.
Journal: Mucosal Immunol
Volume: 4
Issue: 2
Pages: 186-196
eISSN: 1935-3456
DOI: 10.1038/mi.2010.70
Abstract: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.
Source: PubMed
Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia
Authors: Taraban, V.Y., Slebioda, T.J., Willoughby, J.E., Buchan, S.L., James, S., Sheth, B., Smyth, N.R., Thomas, G.J., Wang, E.C.Y. and Al-Shamkhani, A.
Journal: MUCOSAL IMMUNOLOGY
Volume: 4
Issue: 2
Pages: 186-196
eISSN: 1935-3456
ISSN: 1933-0219
DOI: 10.1038/mi.2010.70
Source: Web of Science (Lite)
Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia.
Authors: Taraban, V.Y., Slebioda, T.J., Willoughby, J.E., Buchan, S.L., James, S., Sheth, B., Smyth, N.R., Thomas, G.J., Wang, E.C.Y. and Al-Shamkhani, A.
Journal: Mucosal immunology
Volume: 4
Issue: 2
Pages: 186-196
eISSN: 1935-3456
ISSN: 1933-0219
DOI: 10.1038/mi.2010.70
Abstract: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.
Source: Europe PubMed Central