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Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia

Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia
Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia
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.

1933-0219
186-196
Taraban, V. Y.
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Slebioda, T. J.
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Willoughby, J. E.
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Buchan, S. L.
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James, Sonya
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Sheth, B.
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Smyth, N. R.
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Thomas, G. J.
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Wang, E. C. Y.
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Al-Shamkhani, Aymen
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Taraban, V. Y.
327814dc-b3d7-4291-9fe2-46c88ca19264
Slebioda, T. J.
a6bb8460-652b-4a97-8d97-55630c6a1bf1
Willoughby, J. E.
aaa26cf6-57b9-45f9-9193-a9e5c8d6a025
Buchan, S. L.
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James, Sonya
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Sheth, B.
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Smyth, N. R.
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Thomas, G. J.
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Wang, E. C. Y.
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Al-Shamkhani, Aymen
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Taraban, V. Y., Slebioda, T. J., Willoughby, J. E., Buchan, S. L., James, Sonya, Sheth, B., Smyth, N. R., Thomas, G. J., Wang, E. C. Y. and Al-Shamkhani, Aymen (2011) Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia. Mucosal Immunology, 4, 186-196. (doi:10.1038/mi.2010.70).

Record type: Article

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.

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Taraban et al., 2011.pdf - Accepted Manuscript
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Published date: March 2011
Organisations: Cancer Sciences

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Local EPrints ID: 182343
URI: http://eprints.soton.ac.uk/id/eprint/182343
ISSN: 1933-0219
PURE UUID: 8024864a-4d18-4cb0-bfb3-3db471c2a340
ORCID for Aymen Al-Shamkhani: ORCID iD orcid.org/0000-0003-0727-4189

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Date deposited: 19 Apr 2011 09:41
Last modified: 15 Mar 2024 03:00

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Contributors

Author: V. Y. Taraban
Author: T. J. Slebioda
Author: J. E. Willoughby
Author: S. L. Buchan
Author: Sonya James
Author: B. Sheth
Author: N. R. Smyth
Author: G. J. Thomas
Author: E. C. Y. Wang

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