| First Author | Chen Z | Year | 2022 |
| Journal | Blood | Volume | 139 |
| Issue | 12 | Pages | 1878-1891 |
| PubMed ID | 34871362 | Mgi Jnum | J:346529 |
| Mgi Id | MGI:7616573 | Doi | 1182/blood.2021013474 |
| Citation | Chen Z, et al. (2022) Intestinal IL-33 promotes platelet activity for neutrophil recruitment during acute inflammation. Blood 139(12):1878-1891 |
| abstractText | Peripheral serotonin (5-HT) is mainly generated from the gastrointestinal tract and taken up and stored by platelets in the circulation. Although the gut is recognized as a major immune organ, how intestinal local immune responses control whole-body physiology via 5-HT remains unclear. Here, we show that intestinal inflammation enhances systemic platelet activation and blood coagulation. Intestinal epithelium damage induces elevated levels of the alarm cytokine interleukin-33 (IL-33), leading to platelet activation via promotion of gut-derived 5-HT release. More importantly, we found that loss of intestinal epithelial-derived IL-33 lowers peripheral 5-HT levels, resulting in compromised platelet activation and hemostasis. Functionally, intestinal IL-33 contributes to the recruitment of neutrophils to sites of acute inflammation by enhancing platelet activities. Genetic deletion of intestinal IL-33 or neutralization of peripheral IL-33 protects animals from lipopolysaccharide endotoxic shock through attenuated neutrophil extravasation. Therefore, our data establish a distinct role of intestinal IL-33 in activating platelets by promoting 5-HT release for systemic physiology and inflammation. |
