摘要
Mesenchymal stromal cells (MSCs) are multilineage progenitors with immunomodulatory properties, including expansion of immunomodulatory leukocytes such as regulatory T lymphocytes (Tregs) and tolerogenic dendritic cells. We report that human MSCs can expand CD14-CD11b+CD33 + human myeloid-derived suppressor cells (MDSCs). MSC-expanded MDSCs suppress allogeneic lymphocyte proliferation, express arginase-1 and inducible nitric oxide synthase, and increase the number of Tregs. This expansion occurs through the secretion of hepatocyte growth factor (HGF), with effects replicated by adding HGF singly and abrogated by HGF knockdown in MSCs. In wild-type mice, the liver, which secretes high levels of HGF, contains high numbers of Gr-1+CD11b+ MDSCs, and injection of HGF into mice significantly increases the number of MDSCs. Expansion of MDSCs by MSC-secreted HGF involves c-Met (its receptor) and downstream phosphorylation of STAT3, a key factor in MDSC expansion. Our data further support the strong immunomodulatory nature of MSCs and demonstrate the role of HGF, a mitogenic molecule, in the expansion of MDSCs.
| 原文 | 英語 |
|---|---|
| 頁（從 - 到） | 139-151 |
| 頁數 | 13 |
| 期刊 | Stem Cell Reports |
| 卷 | 1 |
| 發行號 | 2 |
| DOIs | |
| 出版狀態 | 已發佈 - 2013 |
指紋
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Developmental Biology
- Genetics
- Medicine(all)
引用此文
Multipotent human mesenchymal stromal cells mediate expansion of myeloid-derived suppressor cells via hepatocyte growth factor/c-Met and STAT3. / Yen, B. Linju; Yen, Men Luh; Hsu, Pei Ju; Liu, Ko Jiunn; Wang, Chia Jen; Bai, Chyi Huey; Sytwu, Huey Kang.
於: Stem Cell Reports, 卷 1, 編號 2, 2013, p. 139-151.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - Multipotent human mesenchymal stromal cells mediate expansion of myeloid-derived suppressor cells via hepatocyte growth factor/c-Met and STAT3
AU - Yen, B. Linju
AU - Yen, Men Luh
AU - Hsu, Pei Ju
AU - Liu, Ko Jiunn
AU - Wang, Chia Jen
AU - Bai, Chyi Huey
AU - Sytwu, Huey Kang
PY - 2013
Y1 - 2013
N2 - Mesenchymal stromal cells (MSCs) are multilineage progenitors with immunomodulatory properties, including expansion of immunomodulatory leukocytes such as regulatory T lymphocytes (Tregs) and tolerogenic dendritic cells. We report that human MSCs can expand CD14-CD11b+CD33 + human myeloid-derived suppressor cells (MDSCs). MSC-expanded MDSCs suppress allogeneic lymphocyte proliferation, express arginase-1 and inducible nitric oxide synthase, and increase the number of Tregs. This expansion occurs through the secretion of hepatocyte growth factor (HGF), with effects replicated by adding HGF singly and abrogated by HGF knockdown in MSCs. In wild-type mice, the liver, which secretes high levels of HGF, contains high numbers of Gr-1+CD11b+ MDSCs, and injection of HGF into mice significantly increases the number of MDSCs. Expansion of MDSCs by MSC-secreted HGF involves c-Met (its receptor) and downstream phosphorylation of STAT3, a key factor in MDSC expansion. Our data further support the strong immunomodulatory nature of MSCs and demonstrate the role of HGF, a mitogenic molecule, in the expansion of MDSCs.
AB - Mesenchymal stromal cells (MSCs) are multilineage progenitors with immunomodulatory properties, including expansion of immunomodulatory leukocytes such as regulatory T lymphocytes (Tregs) and tolerogenic dendritic cells. We report that human MSCs can expand CD14-CD11b+CD33 + human myeloid-derived suppressor cells (MDSCs). MSC-expanded MDSCs suppress allogeneic lymphocyte proliferation, express arginase-1 and inducible nitric oxide synthase, and increase the number of Tregs. This expansion occurs through the secretion of hepatocyte growth factor (HGF), with effects replicated by adding HGF singly and abrogated by HGF knockdown in MSCs. In wild-type mice, the liver, which secretes high levels of HGF, contains high numbers of Gr-1+CD11b+ MDSCs, and injection of HGF into mice significantly increases the number of MDSCs. Expansion of MDSCs by MSC-secreted HGF involves c-Met (its receptor) and downstream phosphorylation of STAT3, a key factor in MDSC expansion. Our data further support the strong immunomodulatory nature of MSCs and demonstrate the role of HGF, a mitogenic molecule, in the expansion of MDSCs.
UR - http://www.scopus.com/inward/record.url?scp=84881337812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881337812&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2013.06.006
DO - 10.1016/j.stemcr.2013.06.006
M3 - Article
C2 - 24052949
AN - SCOPUS:84881337812
VL - 1
SP - 139
EP - 151
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 2
ER -