Format

Send to

Choose Destination
Stem Cell Res Ther. 2018 Aug 9;9(1):208. doi: 10.1186/s13287-018-0948-4.

Epigenetic modification of mesenchymal stromal cells enhances their suppressive effects on the Th17 responses of cells from rheumatoid arthritis patients.

Author information

1
Convergent Research Consortium for Immunologic Disease, Transplant Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
2
Laboratory of Hematological Disease and Transplant Immunology, The Catholic University of Korea, Seoul, Republic of Korea.
3
Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea.
4
Laboratory of Hematological Disease and Transplant Immunology, The Catholic University of Korea, Seoul, Republic of Korea. yoojink@catholic.ac.kr.
5
Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Republic of Korea. yoojink@catholic.ac.kr.

Abstract

BACKGROUND:

The aim of this study was to investigate if epigenetically modified human mesenchymal stromal cells (hMSCs) can regulate the Th17-related immune responses.

METHODS:

We tested epigenetic drug combinations at various doses and selected the four combinations that resulted in maximal interleukin (IL)-10 and indoleamine 2,3-dioxygenase gene expression in hMSCs. We examined the effects of epigenetically modified hMSCs (epi-hMSCs) on CD4+ T-cell proliferation and inflammatory cytokine secretion under Th0- and Th17-polarizing conditions using mixed lymphocyte reactions and enzyme-linked immunosorbent assays (ELISAs). We determined Th17 cytokine levels and the percentage of Th17 cells among synovial fluid mononuclear cells (SFMCs) from rheumatoid arthritis (RA) patients by ELISA and flow cytometry.

RESULTS:

Epi-hMSCs inhibited the development of IL-17-producing cells in culture. The percentages of IL-17+ and interferon (IFN)-γ+ cells among peripheral blood mononuclear cells from healthy donors were lower under both the Th0 and Th17 conditions in the presence of epi-hMSCs than in the presence of no or untreated hMSCs. Epi-hMSC-treated RA patient SFMCs secreted lower levels of IL-17 and IFN-γ than RA patient SFMCs cultured without hMSCs or with untreated hMSCs.

CONCLUSIONS:

An optimal combination of hypomethylating agents and histone deacetylase inhibitors can enhance the immunomodulatory potential of hMSCs, which may be useful for RA treatment.

KEYWORDS:

Epigenetic modification; Human mesenchymal stromal cells; Rheumatoid arthritis; Th17 cells

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center