Immune status of decidual macrophages is dependent on the CCL2/CCR2/JAK2 pathway during early pregnancy
Chunyan Wei, Ming‐Qing Li, Xiao‐Yong Zhu, Da‐Jin Li
Abstract
Abstract Problem Decidual macrophages (dM φ ) play an important role in the formation of maternal–fetal immune tolerance. However, factors that influence the immune status of dM φ and the related potential mechanisms have not been elucidated to date. Method of study The gene transcription in dM φ , decidual stromal cells (DSCs), extravillous trophoblasts (EVTs), and peripheral monocytes (pMo) from human samples were measured using real‐time polymerase chain reaction (PCR). Monocyte‐DSC co‐culture was established to explore whether DSCs influenced dM φ polarization via C‐C motif ligand 2 (CCL2)‐C‐C chemokine receptor (CCR2) binding using flow cytometry. In vivo, changes in dM φ percentage and M1 and M2 marker expression after treatment with CCR2 or Janus kinase 2 (JAK2) inhibitor were detected with flow cytometry. Embryo resorption percentages in the above groups were also analyzed. Results We found that dM φ were an M1/M2 mixed status at the maternal–fetal interface during early pregnancy. CCL2 influenced the immune status of dM φ in an autocrine and paracrine manner. As a downstream regulator of CCR2 and triggers the Stat3 pathway, JAK2 was found to be essential for dM φ homeostasis in vivo. JAK2 inhibitor decreased the dM φ proportion and attenuated Ki67, CD36, CD86, CD206, TNF, and IL‐10 expression in dM φ at E8.5 d. Moreover, CCR2‐JAK2 pathway inhibition decreased the width of the placental labyrinth layer, further influencing the pregnancy outcome. Conclusion The M1/M2 mixed immune status of dM φ was regulated by DSCs via CCR2, and the CCL2/CCR2/JAK2 pathway was essential for the immune status of dM φ and the outcome of early pregnancy.