MTOR mediates IL-23 induction of neutrophil IL-17 and IL-22 production

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

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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 γ 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.

Original languageEnglish (US)
Pages (from-to)4390-4399
Number of pages10
JournalJournal of Immunology
Volume196
Issue number10
DOIs
StatePublished - May 15 2016

ASJC Scopus subject areas

  • Immunology

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