Invariant NKT cells increase lipopolysacchride-induced pregnancy loss by a mechanism involving Th1 and Th17 responses

Abstract

Objective: To determine the role of invariant natural killer T (iNKT) cells in infection-associated pregnancy loss.

Methods: B6 and iNKT cell-deficient Jα18^−/− mice were injected i.p. with lipopolysaccharide (LPS) or vehicle, and pregnancy outcomes were examined. Decidual iNKT cell expression of CD69 and intracellular cytokine production were analyzed. Mouse decidual iNKT cells were co-cultured with LPS or PBS-treated dendritic cells (DCs), and iNKT cell CD69 expression and intracellular and extracellular cytokine production were assessed.

Results: The embryo resorption rate was notably lessened for Jα18^−/− mice treated with LPS on day 6 or day 9 gestation in comparison with B6 mice treated with LPS. Decidual iNKT cell CD69 expression and intracellular IFN-γ and IL-17 production for B6 mice injected with LPS on day 6 or day 9 gestation were significantly up-regulated compared with PBS-treated mice. Levels of IFN-γ and IL-17 in the supernatants of the co-culture of decidual iNKT cells and LPS-sensitized DCs were strikingly increased in comparison with the co-culture of iNKT cells and PBS-treated DCs. CD69 expression and intracellular IFN-γ and IL-17 production of iNKT cells co-cultured with LPS-sensitized DCs were remarkably up-regulated compared with iNKT cells co-cultured with PBS-treated DCs.

Conclusions: Our results suggest that iNKT cells may play a role in LPS-induced pregnancy loss by Th1 and Th17 cytokine-dependent manner.

• Infection
• iNKT cells
• lipopolysaccharide
• pregnancy loss
• Toll-like receptor