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Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation
INTRODUCTION: Suppressor of cytokine signaling 3 (SOCS3) is a tumour suppressor, limiting intestinal epithelial cell (IEC) proliferation in acute inflammation, and tumour growth, but little is known regarding its role in mucosal homeostasis. Resistance to the intestinal helminth Trichuris muris reli...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569373/ https://www.ncbi.nlm.nih.gov/pubmed/28508554 http://dx.doi.org/10.1002/iid3.171 |
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author | Shaw, Elisabeth J. Smith, Emily E. Whittingham‐Dowd, Jayde Hodges, Matthew D. Else, Kathryn J. Rigby, Rachael J. |
author_facet | Shaw, Elisabeth J. Smith, Emily E. Whittingham‐Dowd, Jayde Hodges, Matthew D. Else, Kathryn J. Rigby, Rachael J. |
author_sort | Shaw, Elisabeth J. |
collection | PubMed |
description | INTRODUCTION: Suppressor of cytokine signaling 3 (SOCS3) is a tumour suppressor, limiting intestinal epithelial cell (IEC) proliferation in acute inflammation, and tumour growth, but little is known regarding its role in mucosal homeostasis. Resistance to the intestinal helminth Trichuris muris relies on an “epithelial escalator” to expel the parasite. IEC turnover is restricted by parasite‐induced indoleamine 2,3‐dioxygenase (IDO). METHODS: Mice with or without conditional knockout of SOCS3 were infected with T. muris. Crypt depth, worm burden, and proliferating cells and IDO were quantified. SOCS3 knockdown was also performed in human IEC cell lines. RESULTS: Chronic T. muris infection increased expression of SOCS3 in wild‐type mice. Lack of IEC SOCS3 led to a modest increase in epithelial turnover. This translated to a lower worm burden, but not complete elimination of the parasite suggesting a compensatory mechanism, possibly IDO, as seen in SOCS3 knockdown. CONCLUSIONS: We report that SOCS3 impacts on IEC turnover following T. muris infection, potentially through enhancement of IDO. IDO may dampen the immune response which can drive IEC hyperproliferation in the absence of SOCS3, demonstrating the intricate interplay of immune signals regulating mucosal homeostasis, and suggesting a novel tumour suppressor role of SOCS3. |
format | Online Article Text |
id | pubmed-5569373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-55693732017-08-29 Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation Shaw, Elisabeth J. Smith, Emily E. Whittingham‐Dowd, Jayde Hodges, Matthew D. Else, Kathryn J. Rigby, Rachael J. Immun Inflamm Dis Original Research INTRODUCTION: Suppressor of cytokine signaling 3 (SOCS3) is a tumour suppressor, limiting intestinal epithelial cell (IEC) proliferation in acute inflammation, and tumour growth, but little is known regarding its role in mucosal homeostasis. Resistance to the intestinal helminth Trichuris muris relies on an “epithelial escalator” to expel the parasite. IEC turnover is restricted by parasite‐induced indoleamine 2,3‐dioxygenase (IDO). METHODS: Mice with or without conditional knockout of SOCS3 were infected with T. muris. Crypt depth, worm burden, and proliferating cells and IDO were quantified. SOCS3 knockdown was also performed in human IEC cell lines. RESULTS: Chronic T. muris infection increased expression of SOCS3 in wild‐type mice. Lack of IEC SOCS3 led to a modest increase in epithelial turnover. This translated to a lower worm burden, but not complete elimination of the parasite suggesting a compensatory mechanism, possibly IDO, as seen in SOCS3 knockdown. CONCLUSIONS: We report that SOCS3 impacts on IEC turnover following T. muris infection, potentially through enhancement of IDO. IDO may dampen the immune response which can drive IEC hyperproliferation in the absence of SOCS3, demonstrating the intricate interplay of immune signals regulating mucosal homeostasis, and suggesting a novel tumour suppressor role of SOCS3. John Wiley and Sons Inc. 2017-05-15 /pmc/articles/PMC5569373/ /pubmed/28508554 http://dx.doi.org/10.1002/iid3.171 Text en © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Shaw, Elisabeth J. Smith, Emily E. Whittingham‐Dowd, Jayde Hodges, Matthew D. Else, Kathryn J. Rigby, Rachael J. Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation |
title | Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation |
title_full | Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation |
title_fullStr | Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation |
title_full_unstemmed | Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation |
title_short | Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation |
title_sort | intestinal epithelial suppressor of cytokine signaling 3 (socs3) impacts on mucosal homeostasis in a model of chronic inflammation |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569373/ https://www.ncbi.nlm.nih.gov/pubmed/28508554 http://dx.doi.org/10.1002/iid3.171 |
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