Immune status of decidual macrophages is dependent on the CCL2/CCR2/JAK2 pathway during early pregnancy

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.

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.

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.

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.