Proposed mechanism of IL-4 enhancement of mouse eosinophil chemotaxis to eotaxin.

<p>Our data showed that the STAT6 and IRS-2 pathways are activated in mouse eosinophils in response to IL-4 (black oval) but to a lesser degree by IL-13. Engagement of CCR3 by eotaxin-1 (white oval) activates G-proteins leading to activation of PI3K isoforms and other signaling pathways. The two pathways may intersect to enhance migration in the activation of Rho guanine nucleotide exchange factors (GEFs), which leads to cytoskeletal rearrangement and enhanced chemotaxis. IL-4/STAT6 has been implicated in spreading/movement of B-cells via Rho GEFs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039673#pone.0039673-Westerberg1" target="_blank">[63]</a>. IL-4 is also known to upregulate adhesion molecules involved in extravasation/chemotaxis – this may be due to activation of STAT6-mediated transcription or activation of the AKT pathway downstream of IRS-2.