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

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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

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Interleukin-23
Interleukin-17
Neutrophils
Colitis
Microbiota
Inflammatory Bowel Diseases
interleukin-22
T-Lymphocytes
Aryl Hydrocarbon Receptors
Retinoids

ASJC Scopus subject areas

  • Immunology

Cite this

MTOR mediates IL-23 induction of neutrophil IL-17 and IL-22 production. / Chen, Feidi; Cao, Anthony; Yao, Suxia; Evans-Marin, Heather L.; Liu, Han; Wu, Wei; Carlsen, Eric D.; Dann-Grice, Sara; Soong, Lynn; Sun, Jiaren; Zhao, Qihong; Cong, Yingzi.

In: Journal of Immunology, Vol. 196, No. 10, 15.05.2016, p. 4390-4399.

Research output: Contribution to journalArticle

Chen, Feidi ; Cao, Anthony ; Yao, Suxia ; Evans-Marin, Heather L. ; Liu, Han ; Wu, Wei ; Carlsen, Eric D. ; Dann-Grice, Sara ; Soong, Lynn ; Sun, Jiaren ; Zhao, Qihong ; Cong, Yingzi. / MTOR mediates IL-23 induction of neutrophil IL-17 and IL-22 production. In: Journal of Immunology. 2016 ; Vol. 196, No. 10. pp. 4390-4399.
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AU - Wu, Wei

AU - Carlsen, Eric D.

AU - Dann-Grice, Sara

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AU - Zhao, Qihong

AU - Cong, Yingzi

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