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

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)295-303
Number of pages9
JournalJournal of Leukocyte Biology
Volume96
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Hepatocyte Growth Factor
Mesenchymal Stromal Cells
Monocytes
T-Lymphocytes
Interleukin-10
Proto-Oncogene Proteins c-met
Cytokines
Phenotype
Adult Stem Cells
Immunomodulation
MAP Kinase Signaling System
Population
Leukocytes
Stem Cells
Spleen
Macrophages
Cell Proliferation

Keywords

  • Th1/2 cytokine

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Induction of immunomodulatory monocytes by human mesenchymal stem cell-derived hepatocyte growth factor through ERK1/2. / Chen, Pei Min; Liu, Ko Jiunn; Hsu, Pei Ju; Wei, Chung Fan; Bai, Chyi Huey; Ho, Ling Jun; Sytwu, Huey Kang; Linju Yen, B.

In: Journal of Leukocyte Biology, Vol. 96, No. 2, 2014, p. 295-303.

Research output: Contribution to journalArticle

Chen, Pei Min ; Liu, Ko Jiunn ; Hsu, Pei Ju ; Wei, Chung Fan ; Bai, Chyi Huey ; Ho, Ling Jun ; Sytwu, Huey Kang ; Linju Yen, B. / Induction of immunomodulatory monocytes by human mesenchymal stem cell-derived hepatocyte growth factor through ERK1/2. In: Journal of Leukocyte Biology. 2014 ; Vol. 96, No. 2. pp. 295-303.
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