title: IL-17 down-regulates the immunosuppressive capacity of olfactory ecto-mesenchymal stem cells in murine collagen-induced arthritis.
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.
authors.affiliation: Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.|Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.|Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Rui
authors.affiliation: Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Tang
authors.affiliation: Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Tian
authors.affiliation: Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Yungang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pathology and Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.|Institute of Laboratory Medicine, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D008811:Mice, Inbred DBA; D009831:Olfactory Mucosa / Q000166:cytology*; D034622:RNA Interference; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17
keywords: IL-17; Immune response; Immunity; Immunology and Microbiology Section; Treg; collagen-induced arthritis; olfactory ecto-mesenchymal stem cells; suppressive capacity