Chemokine blockade

A fetus must be sheltered from any inflammatory battle taking place in the mother. Now, Yeny Martinez de la Torre, Alberto Mantovani (University of Milan, Italy), and colleagues report that a decoy receptor in the placenta captures potentially dangerous pro-inflammatory chemokines from the mother. This scavenging suppresses inflammation and prevents fetal loss.

Decoy receptors such as the D6 receptor bind many inflammatory chemokines without activating intracellular signaling. Instead, the receptor and chemokine are internalized and the chemokine is destroyed.

The Italian group confirmed that D6 is expressed in the placenta, specifically on the apical side of syncytial trophoblasts. This is the side looking at the maternal blood and thus “a strategic location at the very interface between mother and fetus,” says Mantovani.

To test the function of D6, the team injected pro-inflammatory LPS. The response was greater in mice lacking D6: several inflammatory chemokines built to higher levels in the circulation and placenta; more macrophages and T lymphocytes invaded the placenta; and there was more fetal loss.

Fetal loss may occur after a deadly positive feedback between inflammation and blood clotting in the placenta. In the mice lacking D6, this can be prevented with an infusion of anti-chemokine antibodies. A similar blocking approach may be possible in some humans who suffer from recurrent fetal loss, although it is not yet clear whether changes in D6 function are implicated in any of these individuals.

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