Regulation of allergic inflammation by murine endothelial cell transglutaminase 2 (HYP7P.260)

Abstract

Tissue transglutaminase 2 (TG2) is a multifunctional enzyme that is involved in inflammatory processes. In allergic inflammation, previous research indicates that TG2 is upregulated in human asthma and in the lung endothelium of OVA-challenged mice. We hypothesized that endothelial cell TG2 is required for allergic inflammation. To test this hypothesis, we generated mice in which TG2 was specifically deleted in the endothelium using the Cre-Lox recombinase system. To induce allergic inflammation, mice were sensitized and challenged with OVA. Compared to wild type mice challenged with OVA, OVA-challenged TG2 knockout mice exhibited a significant reduction in lung airway resistance, the number of eosinophils in the BAL, and the number of eosinophils in the airway spaces. Endothelial deletion of TG2 did not affect chemokines and cytokines that regulate allergic inflammation. Taken together, these findings indicate that endothelial cell TG2 is required for allergic inflammation. This suggests that TG2 regulates the recruitment of eosinophils into OVA-challenged lungs. Future studies will focus on identifying mechanisms by which TG2 regulates signals for leukocyte recruitment during allergic lung inflammation.