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

Problem To explore whether IL ‐33/ ST 2 axis modulates the polarization and efferocytosis of decidual macrophages ( dM φs). Method of study The phenotype characteristics of dM φs 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 ( ST 2) in dM φs were analyzed by FCM . Finally, the effects of sST 2, a decoy receptor for IL ‐33 that inhibits the IL ‐33/ ST 2 signaling pathway, on the polarization and efferocytosis of dM φs and human macrophage cell line U937 were investigated. Results 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, dM φs from RSA patients possessed a more powerful efferocytosis ability to clear the apoptotic decidual stromal cells ( DSC s) compared with dM φs from normal pregnancy patients. Treatment with recombinant human sST 2 led to the up‐regulation of M1 bias and efferocytosis ability of both normal dM φs and U937. Conclusion This study indicates that IL ‐33 secreted by dM φs promotes M2 bias at the feto‐maternal interface, and as a result, RSA might attribute to the disturbance of IL ‐33/ ST 2 axis and the enhancement of efferocytosis of dM φs subsequently.