mTOR Mediates IL-23 Induction of Neutrophil IL-17 and IL-22 Production

作者：Chen, Feidi; Cao, Anthony; Yao, Suxia; Evans-Marin, Heather L.; Liu, Han; Wu, Wei; Carlsen, Eric D.; Dann, Sara M.; Soong, Lynn; Sun, Jiaren; Zhao, Qihong; Cong, Yingzi^*

来源：The Journal of Immunology, 2016, 196(10): 4390-4399.

DOI：10.4049/jimmunol.1501541

• ROR-GAMMA-T
• INTERLEUKIN 17A
• TH17 CELLS
• INFLAMMATION
• EXPRESSION
• COLITIS
• ACTIVATION
• AUTOPHAGY
• DEPLETION
• DISEASE

It has been shown recently that neutrophils are able to produce IL-22 and IL-17, which differentially regulate the pathogenesis of inflammatory bowel disease. However, it is still largely unknown how the neutrophil production of IL-22 and IL-17 is regulated, and their role in the pathogenesis of inflammatory bowel disease. In this study, we found that IL-23 promoted neutrophil production of IL-17 and IL-22. IL-23 stimulated the neutrophil expression of IL-23R as well as rorc and ahr. Retinoid acid receptor-related orphan receptor gamma t and aryl-hydrocarbon receptor differentially regulated IL-23 induction of neutrophil IL-17 and IL-22. In addition, IL-23 induced the activation of mTOR in neutrophils. Blockade of the mTOR pathway inhibited IL-23-induced expression of rorc and ahr, as well as IL-17 and IL-22 production. By using a microbiota Ag-specific T cell-mediated colitis model, we demonstrated that depletion of neutrophils, as well as blockade of IL-22, resulted in a significant increase in the severity of colitis, thereby indicating a protective role of neutrophils and IL-22 in chronic colitis. Collectively, our data revealed that neutrophils negatively regulate microbiota Ag-specific T cell induction of colitis, and IL-23 induces neutrophil production of IL-22 and IL-17 through induction of rorc and ahr, which is mediated by the mTOR pathway.

• 出版日期2016-5-15
• 单位山东大学; 同济大学