Role of CCL22 in human spontaneous and repeated miscarriage

Treg are a subpopulation of T cells with the capacity of down-regulating the immune response. Infiltration of tissues with Treg is thus associated with immune tolerance. This could be particularly important for the tolerance of the fetus in pregnancy. Several chemokines were described to be responsible for Treg accumulation in human and therefore, potentially play a role in human spontaneous and repeated miscarriage. CCL22 has been described to recruit Treg in human normal and pathological tissues. We found that CCL22 specifically recruits human Tregs in vitro.

We aimed to investigate whether CCL22 is expressed in human placenta in order to evaluate whether this chemokine may be involved in the recruitment of Treg in the pregnancy. 30 paraffin samples of human placenta (10 control, 10 spontaneous abortion, 10 repeated miscarriages) were stained for CCL22 and the expression level was evaluated in a semi-quantitative manner (IRS score).

We found that all human placenta samples expressed CCL22 at the interface between fetal tissue and maternal blood (syncytiotrophoblast). But CCL22 expression in the extravillous trophoblast was only observed in spontaneous as well as repeated miscarriage samples. In most of the cases, extravillous trophoblast cells themselves seem to express CCL22. However also immune cells, like macrophages could possibly also express CCL22.

Our results demonstrate that CCL22, a chemokine that specifically attracts Treg, is expressed in human placenta. The expression in the extravillous trophoblast was only observed in miscarriage samples. Therefore, it will be interesting to further evaluate this chemokine for his role in this pathology.