IL-33/ST2 axis affects the polarization and efferocytosis of decidual macrophages in early pregnancy

To explore whether IL-33/ST2 axis modulates the polarization and efferocytosis of decidual macrophages (dMφs).

The phenotype characteristics of dMφs from both normal pregnant women and recurrent spontaneous abortion (RSA) patients were determined by real-time polymerase chain reaction (RT-PCR) and flow cytometry (FCM). Then, the efferocytosis and expression of IL-33 and its receptor (ST2) in dMφs were analyzed by FCM. Finally, the effects of sST2, a decoy receptor for IL-33 that inhibits the IL-33/ST2 signaling pathway, on the polarization and efferocytosis of dMφs and human macrophage cell line U937 were investigated.

Compared with normal pregnancy, dMφs from RSA patients presented a M1 phenotype with high secretion of IL-33, whereas the expression of ST2 decreased. However, dMφs from RSA patients possessed a more powerful efferocytosis ability to clear the apoptotic decidual stromal cells (DSCs) compared with dMφs from normal pregnancy patients. Treatment with recombinant human sST2 led to the up-regulation of M1 bias and efferocytosis ability of both normal dMφs and U937.

This study indicates that IL-33 secreted by dMφs promotes M2 bias at the feto-maternal interface, and as a result, RSA might attribute to the disturbance of IL-33/ST2 axis and the enhancement of efferocytosis of dMφs subsequently.