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

Pei Min Chen, Ko Jiunn Liu, Pei Ju Hsu, Chung Fan Wei, Chyi Huey Bai, Ling Jun Ho, Huey Kang Sytwu, B. Linju Yen

研究成果: 雜誌貢獻文章

57 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)295-303
頁數9
期刊Journal of Leukocyte Biology
96
發行號2
DOIs
出版狀態已發佈 - 2014

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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