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Sci Rep. 2018 Jan 11;8(1):427. doi: 10.1038/s41598-017-18693-0.

Loss of A20 in BM-MSCs regulates the Th17/Treg balance in Rheumatoid Arthritis.

Feng Z1,2,3, Zhai Y1,2,3, Zheng Z1,3, Yang L4, Luo X1,3, Dong X1,2,3, Han Q1,3, Jin J2,3, Chen ZN5,6, Zhu P7,8.

Author information

1
Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.
2
Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
3
National Translational Science Center for Molecular Medicine, Xi'an, 710032, China.
4
Department of hematology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.
5
Department of Cell Biology, Fourth Military Medical University, Xi'an, China. znchen@fmmu.edu.cn.
6
National Translational Science Center for Molecular Medicine, Xi'an, 710032, China. znchen@fmmu.edu.cn.
7
Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China. zhuping@fmmu.edu.cn.
8
National Translational Science Center for Molecular Medicine, Xi'an, 710032, China. zhuping@fmmu.edu.cn.

Abstract

Mesenchymal stem cells (MSCs) are multi-potent cells that are self-renewable and possess the potential to differentiate into multiple lineages. Several studies demonstrated that MSCs could regulate a Th17/Treg balance and could be a potential therapeutic target for Rheumatoid Arthritis (RA). A20 is highly expressed in many cell types after the stimulation of TNF-α, where it may inhibit pro-inflammatory cytokine secretion. However, the expression of A20 in BM-MSCs in RA is not fully understood. In our study, we found that A20 was decreased in RA patients' bone marrow MSCs (BM-MSCs), and with more IL-6 secretion, the balance of Th17/Treg was broken. In CIA mice, we found a moderate A20 decrease in mice MSCs as compared with those of control group in mRNA and protein levels. However, the IL-6 expression was increased. After umbilical cord MSCs treatment, A20 and IL-6 expressions were equal to the control group. Thus, our study indicates that loss of A20 in MSCs regulates the Th17/Treg balance in RA and the regulatory role of A20 in pro-inflammatory IL-6 production could be a potential target for the transfer of MSCs in RA adoptive therapy.

PMID:
29323140
PMCID:
PMC5765124
DOI:
10.1038/s41598-017-18693-0
[Indexed for MEDLINE]
Free PMC Article

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