The decidual stromal cells-secreted CCL2 induces and maintains decidual leukocytes into Th2 bias in human early pregnancy

Clin Immunol. 2012 Nov;145(2):161-73. doi: 10.1016/j.clim.2012.07.017. Epub 2012 Aug 14.

Abstract

The precise mechanism of characteristic Th2 predominance at maternal-fetal interface remains unresolved. In the present study, we investigated roles of the decidua-derived CCL2 in Th2 predominance at maternal-fetal interface. FCM shows that 55% CD56(+)CD16(-)CD3(-) decidual NK, 52% CD4(+) T cells and 75% CD14(+) monocytes express CCR2. Recombinant human CCL2 (rhCCL2) and the decidual stromal cells (DSCs)-derived supernatant can enhance proliferation and inhibit apoptosis of these decidual leukocytes (DLCs), and promote Th2 cytokines production, IL-4 and IL-10, with an increase in GATA-3 transcription. They also inhibit the secretion of Th1 cytokines, TNF-α and IFN-γ, with a decrease in T-bet transcription It is concluded that the secreted CCL2 by decidual stromal cells increases GATA-3 transcription and decreases T-bet transcription in the decidual leukocytes, which contributes to Th2 polarization at maternal-fetal interface. Furthermore, the Th2 cytokines, IL-4 and IL-10, rather than Th1 cytokines, was shown to increase CCL2 secretion of DSC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Proliferation / drug effects
  • Chemokine CCL2 / immunology*
  • Chemokine CCL2 / metabolism
  • Chemokine CCL2 / pharmacology
  • Culture Media, Conditioned
  • Decidua / cytology
  • Decidua / drug effects*
  • Decidua / immunology
  • Female
  • GATA3 Transcription Factor / agonists
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Pregnancy / immunology*
  • Pregnancy Trimester, First
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / immunology
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • Stromal Cells / cytology
  • Stromal Cells / immunology
  • Stromal Cells / metabolism*
  • Th1-Th2 Balance / drug effects
  • Th2 Cells / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Transcription, Genetic

Substances

  • Antigens, CD
  • CCL2 protein, human
  • CCR2 protein, human
  • Chemokine CCL2
  • Culture Media, Conditioned
  • GATA3 Transcription Factor
  • Receptors, CCR2
  • Recombinant Proteins