*gestures, exasperated*
Ugh, again?! Francis Fukuyama assured me this was over.

This paper reveals a novel mechanism by which Siglec function is regulated and suggests that mast cells can be depleted through Siglec-8 ligation following the disruption of cis ligand interactions.

Notably, we show that Siglec-8 is capable of inducing the cell death of primary human mast cells (skin-derived, in this case), which is potentiated by the enzymatic removal of cell-surface sialic acid.

The cell death pathway resembles that licensed by IL-5 priming in that it leads to CD11b upregulation at the cell surface, ROS generation, and is dependent on the signaling activities of PI3K, PLC, and Syk.

However, this paper is the first to show that these interactions impact Siglec-8 function (independent of binding!). Enzymatic removal of alpha-2,3-linked sialic acid from the cell surface enables cell death induction in response to anti-Siglec-8 mAb without the need for cytokine priming.

We had previously shown that Siglec-8 is partially masked on eosinophils by interactions with sialylated cis ligands: www.jacionline.org/article/S009...