Expression of C-type lectin receptors and Toll-like receptors in decidua of patients with unexplained recurrent spontaneous abortion.

Abstract

In the present study, the mechanisms underlying the pathogenesis of unexplained recurrent spontaneous abortion (URSA) were explored. The protein and mRNA expression of two C-type lectin-like receptors (CLRs), namely dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and mannose receptor (MR), and two Toll-like receptors (TLRs), namely TLR2 and TLR4, in the decidua and dendritic cells (DCs) was compared between URSA patients and normal controls. URSA patients had significantly lower protein and mRNA expression of DC-SIGN and significantly higher expression of TLR2 and TLR4 in decidual tissues compared with normal controls. In addition, URSA patients had significantly higher levels of the T helper (Th) 1 cytokines interleukin (IL)-2 and interferon-γ, and significantly lower levels of the Th2 cytokines IL-10 and transforming growth factor β1 in decidual tissues compared with the control group. The TLR2 agonist synthetic triacylated lipoprotein (Pam3CSK4) and the TLR4 agonist lipopolysaccharide were used to demonstrate that TLR2 and TLR4 modulate Th1/Th2 cytokine imbalance in DC-T cell cocultures. The results suggest that the balance between CLRs and TLRs was tilted towards a TLR-dominant response in URSA patients, which may disrupt maternal-fetal immune tolerance, resulting in spontaneous abortion.