Intestinal IL-33 promotes platelet activity for neutrophil recruitment during acute inflammation.
Blood
; 139(12): 1878-1891, 2022 03 24.
Article
em En
| MEDLINE
| ID: mdl-34871362
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Serotonina
/
Interleucina-33
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article