期刊
EXPERIMENTAL CELL RESEARCH
卷 316, 期 19, 页码 3109-3123出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2010.08.008
关键词
Mesenchymal stromal cells; Immunosuppressive properties; Prostaglandin E2; Dendritic cells; T lymphocytes
资金
- Grupo de Biociencias de la Comunidad de Madrid (MESENCAM) [S2006/BIO-0204]
- Instituto de Salud Carlos III (RETIC-TERCEL) [RD06/0010/0015]
- Ministerio de Ciencias e Inovacion (AIM) [PS-010000-2009-2]
- Instituto de Salud Carlos III [PS09/01026]
Mesenchymal stromal cells (MSCs) have important immunosuppressive properties, but the mechanisms and soluble factors involved in these effects remain unclear. We have studied prostaglandin-E2 (PGE2) as a possible candidate implied in adipose tissue-derived MSCs (Ad-MSCs) immunosuppressive properties over dendritic cells and T lymphocytes, compared to bone marrow derived MSCs (BM-MSCs). We found that both MSCs inhibited the maturation of myeloid-DCs and plasmocytoid-DCs. High levels of PGE2 were detected in DCs/MSCs co-cultures. Its blockade with indomethacin (IDM) allowed plasmocytoid-DCs but not myeloid-DCs maturation. Additionally, high levels of PGE2 were found in co-cultures in which Ad-MSCs or BM-MSCs inhibited activated T cells proliferation and pro-inflammatory cytokines production. PGE2 blockade by IDM preserved T lymphocytes proliferation but did not restore the pro-inflammatory cytokines secretion. However, an increased expression of transcription factors and cytokines genes involved in the Th1/Th2 differentiation pathway was detected in the T cells co-cultured with Ad-MSCs, but not with BM-MSCs. In conclusion, we propose that PGE2 is a soluble factor mediating most of the immunosuppressive effects of Ad-MSCs and BM-MSCs over p-DCs maturation and activated T lymphocytes proliferation and cytokine secretion. (C) 2010 Elsevier Inc. All rights reserved.
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