Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation.

Shaw, Elisabeth Jane and Smith, Emily and Whittingham-Dowd, Jayde Kathleen and Hodges, Matthew David John and Else, Kathryn J. and Rigby, Rachael Jane (2017) Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on mucosal homeostasis in a model of chronic inflammation. Immunity, Inflammation and Disease, 5 (3). pp. 336-345. ISSN 2050-4527

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Abstract

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.

Item Type:
Journal Article
Journal or Publication Title:
Immunity, Inflammation and Disease
ID Code:
86350
Deposited By:
Deposited On:
17 May 2017 14:34
Refereed?:
Yes
Published?:
Published
Last Modified:
23 Sep 2020 03:31