Decidual natural killer （dNK） cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early preg...Decidual natural killer （dNK） cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early pregnancy. However, the mechanism for how the dNK cells play such important roles in successful pregnancy remains undefined. Here, we identified a subtype of dNK cells characterized as having a CD3-CD56^brightCD25^＋ phenotype. We found that CD56^brightCD25^＋ NK cells preferentially localize to the maternal/fetal interface during early human pregnancy. CD25^＋ dNK cells account for approximately 75% of CD25-expressing decidual immune cells （DICs）. However, less than 5% of CD25-positive peripheral blood mononuclear cells are CD25^＋ NK cells. Furthermore, CD25^＋ and CD25^- dNK cells exhibit distinct phenotypes： CD25^＋ dNK cells display a more activated phenotype and greater cytokine-secreting capacity. Interestingly, coculture of peripheral NK （pNK） cells with primary trophoblasts upregulates the percentage of CD25-expressing pNK cells, resulting in increased expression of activation markers and cytokine production by pNK cells. In addition, we demonstrated that the CXCL12/CXCR4 axis is crucial for the recruitment of CD25^＋ dNK cells and contributes to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells at the maternal/fetal interface. Thus, our data reveal that the crosstalk between trophoblasts and pNK cells leads to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells, which exert a regulating effect at the maternal/fetal interface.展开更多
基金This work was supported by the Key Project of Shanghai Basic Research from Shanghai Municipal Science and Technology Commission （STCSM） （12JC1401600 to DJL）, the Key Project of Shanghai Municipal Education Commission （MECSM） （14ZZ013 to MRD） and the Nature Science Foundation from National Nature Science Foundation of China （NSFC） （NSFC31270969 to DJL NSFC81070537, NSFC31171437 and NSFC81370770 to MRD+1 种基金 NSFC31300751 to HLP NSFC81370730 to QF）.
文摘Decidual natural killer （dNK） cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early pregnancy. However, the mechanism for how the dNK cells play such important roles in successful pregnancy remains undefined. Here, we identified a subtype of dNK cells characterized as having a CD3-CD56^brightCD25^＋ phenotype. We found that CD56^brightCD25^＋ NK cells preferentially localize to the maternal/fetal interface during early human pregnancy. CD25^＋ dNK cells account for approximately 75% of CD25-expressing decidual immune cells （DICs）. However, less than 5% of CD25-positive peripheral blood mononuclear cells are CD25^＋ NK cells. Furthermore, CD25^＋ and CD25^- dNK cells exhibit distinct phenotypes： CD25^＋ dNK cells display a more activated phenotype and greater cytokine-secreting capacity. Interestingly, coculture of peripheral NK （pNK） cells with primary trophoblasts upregulates the percentage of CD25-expressing pNK cells, resulting in increased expression of activation markers and cytokine production by pNK cells. In addition, we demonstrated that the CXCL12/CXCR4 axis is crucial for the recruitment of CD25^＋ dNK cells and contributes to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells at the maternal/fetal interface. Thus, our data reveal that the crosstalk between trophoblasts and pNK cells leads to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells, which exert a regulating effect at the maternal/fetal interface.
