IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function.
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| Abstract |
Vertebrate immunity has evolved a modular architecture in response to perturbations. Allergic inflammation represents such a module, with signature features of antigen-specific IgE and tissue eosinophilia, although the cellular and molecular circuitry coupling these responses remains unclear. Here, we use genetic and imaging approaches in models of IgE-dependent eosinophilic dermatitis to demonstrate a requisite role for basophils. After antigenic inflammation, basophils initiate transmigration like other granulocytes but, upon activation via their high-affinity IgE receptor, alter their migratory kinetics to persist at the endothelium. Prolonged basophil-endothelial interactions, in part dependent on activation of focal adhesion kinases, promote delivery of basophil-derived IL-4 to the endothelium and subsequent induction of endothelial vascular cell adhesion molecule-1 (VCAM-1), which is required for eosinophil accumulation. Thus, basophils are gatekeepers that link adaptive immunity with innate effector programs by altering access to tissue sites by activation-induced interactions with the endothelium.
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| Authors | Laurence E Cheng, Brandon M Sullivan, Lizett E Retana, Christopher D C Allen, Hong-Erh Liang, Richard M Locksley |
| Journal | The Journal of experimental medicine (J Exp Med) Vol. 212 Issue 4 Pg. 513-24 (Apr 06 2015) ISSN: 1540-9538 [Electronic] United States |
| PMID | 25779634 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | © 2015 Cheng et al. |
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