Inappropriate activation of invariant natural killer T cells and antigen-presenting cells with the elevation of HMGB1 in preterm births without acute chorioamnionitis

Problem Acute chorioamnionitis (aCAM) associated with microbial infection is a primary cause of preterm birth (PB). However, recent studies have demonstrated that innate immunity and sterile inflammation are causes of PB in the absence of aCAM. Therefore, we analyzed immune cells in the decidua of early to moderate PB without aCAM. Method of study Deciduas were obtained from patients with PB at a gestational age of 24(+0)to 33(+6) weeks without aCAM in pathological diagnosis. The patients were divided into two groups as follows: patients with labor and/or rupture of membrane (ROM) (no aCAM with labor and/or ROM: nCAM-w-LR), and patients without labor and/or ROM (no aCAM without labor and/or ROM: nCAM-w/o-LR). The immune cells and high mobility group box 1 (HMGB1) levels in the decidua were analyzed using flow cytometry. Co-culture of CD56(+)cells with dendritic cells (DCs) and macrophages obtained from the decidua was also performed in the presence of HMGB1. Results The nCAM-w-LR group demonstrated an accumulation of iNKT cells, and increased expression of HMGB1, TLR4, receptors for advanced glycation end products, and CD1d on DCs and macrophages. HMGB1 facilitated the proliferation of iNKT cells co-cultured with DCs and macrophages, which was found to be inhibited by heparin. Conclusions Inappropriate activation of innate immune cells and increased HMGB1 expression may represent parturition signs in human pregnancy. Therefore, control of these cells and HMGB1 antigenicity may be represent a potential therapeutic target for the prevention of PB.

Automated summary

The study found that inappropriate activation of innate immune cells and increased HMGB1 expression in the decidua of preterm birth patients without acute chorioamnionitis may serve as signs of parturition in human pregnancy. Therefore, controlling these cells and HMGB1 antigenicity may represent a potential therapeutic target for the prevention of preterm birth.