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

Problem: To explore whether IL-33/ST2 axis modulates the polarization and efferocytosis of decidual macrophages (dM phi s). Method of study: The phenotype characteristics of dM phi s 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 dM phi s 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 dM phi s and human macrophage cell line U937 were investigated. Results: Compared with normal pregnancy, dM phi s from RSA patients presented a M1 phenotype with high secretion of IL-33, whereas the expression of ST2 decreased. However, dM phi s from RSA patients possessed a more powerful efferocytosis ability to clear the apoptotic decidual stromal cells (DSCs) compared with dM phi s from normal pregnancy patients. Treatment with recombinant human sST2 led to the up-regulation of M1 bias and efferocytosis ability of both normal dM phi s and U937. Conclusion: This study indicates that IL-33 secreted by dM phi s 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 dM phi s subsequently.