Oncotarget

Research Papers: Immunology:

IL-17 down-regulates the immunosuppressive capacity of olfactory ecto-mesenchymal stem cells in murine collagen-induced arthritis

Jie Tian, Ke Rui, Xinyi Tang, Wenxin Wang, Jie Ma, Xinyu Tian, Yungang Wang, Huaxi Xu, Liwei Lu and Shengjun Wang _

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Oncotarget. 2016; 7:42953-42962. https://doi.org/10.18632/oncotarget.10261

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Abstract

Jie Tian1,2,*, Ke Rui1,2,*, Xinyi Tang1,*, Wenxin Wang2, Jie Ma2, Xinyu Tian2, Yungang Wang2, Huaxi Xu2, Liwei Lu3 and Shengjun Wang1,2

1 Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China

2 Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University, Zhenjiang, China

3 Department of Pathology and Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China

* These authors have contributed equally to this work

Correspondence to:

Shengjun Wang, email:

Liwei Lu, email:

Huaxi Xu, email:

Keywords: olfactory ecto-mesenchymal stem cells, IL-17, suppressive capacity, Treg, collagen-induced arthritis, Immunology and Microbiology Section, Immune response, Immunity

Received: May 11, 2016 Accepted: June 13, 2016 Published: June 23, 2016

Abstract

Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a population of cells which has been recognized as a new resident stem cell type in the olfactory lamina propria. OE-MSCs have been shown to exert their immunosuppressive capacity by modulating T cell responses, including up-regulation of regulatory T cells (Tregs) and down-regulation of Th1/Th17 cells. As an inflammatory cytokine, IL-17 plays a critical role in orchestrating the inflammatory response during the development of collagen-induced arthritis (CIA). However, it is unclear whether the increased level of IL-17 may affect the immunosuppressive function of OE-MSCs under inflammatory condition. In this study, we found that IL-17 could significantly reduce the suppressive capacity of OE-MSCs on CD4+ T cells and down-regulate the suppressive factors produced by OE-MSCs. Notably, IL-17 treatment abolished the capacity of OE-MSCs in inducing Treg expansion. In addition, knockdown of IL-17R in OE-MSCs significantly enhanced their therapeutic effect in ameliorating CIA upon adoptive transfer. Moreover, IL-17R knockdown-OE-MSCs could efficiently induce Tregs expansion and reduce Th1 and Th17 responses. Taken together, all these data suggest that IL-17R knockdown in OE-MSCs may provide a novel strategy in maintaining their immunosuppressive properties for the treatment of autoimmune diseases.


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