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  • Induction of immunomodulatory monocytes by human mesenchymal stem cell-derived hepatocyte growth factor through ERK1/2.

Induction of immunomodulatory monocytes by human mesenchymal stem cell-derived hepatocyte growth factor through ERK1/2.

Journal of leukocyte biology (2014-04-10)
Pei-Min Chen, Ko-Jiunn Liu, Pei-Ju Hsu, Chung-Fan Wei, Chyi-Huey Bai, Ling-Jun Ho, Huey-Kang Sytwu, B Linju Yen
ABSTRACT

Monocytes are a population of leukocytes that terminally differentiate into macrophages and DCs. Whereas these differentiated progeny have inflammatory and resident--which are more immunomodulatory--phenotypes, less has been reported on the plasticity of monocytes themselves. We found that MSCs, a population of somatic stem cells, can rapidly induce human and murine monocytes through secretion of HGF to acquire an immunomodulatory phenotype to suppress T cell effector function. MSCs are multilineage postnatal progenitor cells with strong immunomodulatory effects toward T lymphocytes, NK lymphocytes, and DCs, but less is known regarding their interactions with monocytes. We found that CD14(+) human monocytes express c-Met, the receptor for HGF, and both depletion of HGF-treated CD14(+) monocytes and knockdown of HGF secretion in MSCs abrogate the suppression of anti-CD3/28-activated T cell proliferation. HGF-treated monocytes remain undifferentiated and can alter activated T cell cytokine expression from a Th1 toward Th2 profile. Moreover, monocytes cocultured with MSCs or treated with HGF alone can produce high levels of IL-10, a potent immunomodulatory cytokine. Injection of HGF to WT mice also results in an increase in IL-10(+)-expressing monocytes from the spleen, a known reservoir for circulating monocytes. Mechanistically, HGFs modulate IL-10 production in monocytes through the ERK1/2 pathway. Our data demonstrate further the pleomorphic nature of MSC immunomodulation, as well as highlight the important role of immunomodulatory monocytes in altering T cell effector function.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
5-Carboxy-fluorescein diacetate N-succinimidyl ester, for fluorescence, ≥95.0% (HPLC)
Sigma-Aldrich
5(6)-Carboxyfluorescein diacetate N-succinimidyl ester, BioReagent, suitable for fluorescence, ≥90% (HPLC)
Sigma-Aldrich
Human MET / Hepatocyte Growth Factor Receptor ELISA Kit
Sigma-Aldrich
Phosphotyrosine MET / Hepatocyte Growth Factor Receptor ELISA Kit
Sigma-Aldrich
Mouse HGF ELISA Kit, for cell and tissue lysates
Sigma-Aldrich
Human HGF ELISA Kit, for cell and tissue lysates
Sigma-Aldrich
Human HGF ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Mouse HGF ELISA Kit, for serum, plasma and cell culture supernatant