Intestinal IL-33 promotes platelet activity for neutrophil recruitment during acute inflammation

Abstract

The peripheral serotonin (5-HT) is mainly generated from the gastrointestinal tract, and taken up and stored by platelets in the circulation. While the gut is recognized as a major immune organ, how intestinal local immune responses control whole body physiology via 5-HT is yet unclear. Here, we show that intestinal inflammation enhances systemic platelet activation and blood coagulation. Intestinal epithelium damage induces the elevated level of alarm cytokine interleukin-33 (IL-33), leading to platelet activation via promoting gut-derived 5-HT release. More importantly, we found that loss of intestinal epithelial-derived IL-33 dampens peripheral 5-HT level, resulting in compromised platelet activation and hemostasis. Functionally, intestinal IL-33 contributes to the recruitment of neutrophils to the sites of acute inflammation by enhancing platelet activities. Genetical deletion of intestinal IL-33 or neutralization of peripheral IL-33, protects the animals from lipopolysaccharide endotoxic shock owing to attenuated neutrophil extravasation. Therefore, our data establish a distinct role of intestinal IL-33 in activating platelet by promoting 5-HT release for systemic physiology and inflammation.