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Regulatory T cells decrease invariant natural killer T cell-mediated pregnancy loss in mice.

L Li1, J Tu1, Y Jiang1

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Stimulating invariant natural killer T (iNKT) cells with α-galactosylceramide (αGC) causes pregnancy loss in mice. This occurs via interferon-gamma (IFN-γ) and impaired regulatory T (Treg) cell function.

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Area of Science:

  • Immunology
  • Reproductive Biology
  • Developmental Biology

Background:

  • Pregnancy loss is a common complication with poorly understood causes.
  • Invariant natural killer T (iNKT) cells and regulatory T (Treg) cells are implicated in reproductive outcomes.

Purpose of the Study:

  • To investigate the mechanisms of iNKT cell-mediated pregnancy loss.
  • To elucidate the role of Treg cells in this process.

Main Methods:

  • Mice were treated with α-galactosylceramide (αGC) to stimulate iNKT cells.
  • Fetal resorption, immune cell populations (iNKT, Treg), cytokine levels (IL-10, TGF-β, IFN-γ, TNF-α, IL-4), and cell co-cultures were analyzed.
  • Adoptive transfers of iNKT and Treg cells were performed in iNKT cell-deficient mice.

Main Results:

  • αGC administration induced fetal resorption, activated decidual iNKT cells, and decreased decidual Treg cells and their suppressive cytokines (IL-10, TGF-β).
  • Pregnancy loss was dependent on IFN-γ production by iNKT cells, as IFN-γ knockout mice were protected.
  • Adoptive transfer of Treg cells ameliorated αGC-induced pregnancy loss, while iNKT cells restored it in deficient mice.

Conclusions:

  • iNKT cell activation leads to pregnancy loss in mice, dependent on IFN-γ.
  • Impaired Treg cell function and reduced IL-10/TGF-β production by Treg cells are critical in iNKT cell-mediated pregnancy loss.