Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion

Celia Peral de Castro, Sarah A Jones, Cliona Ni Cheallaigh, Claire A Hearnden, Laura K Williams, Jan Winter, Ed C Lavelle, Kingston H G Mills, James Harris

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116 Citations (Scopus)


Autophagy controls IL-1beta secretion by regulating inflammasome activation and by targeting pro-IL-1beta for degradation. In this article, we show that inhibition of autophagy, either with the PI3K inhibitors 3-methyladenine, wortmannin, and LY294002 or with small interfering RNA against autophagy proteins augmented the secretion of IL-23 by human and mouse macrophages and dendritic cells in response to specific TLR agonists. This process occurred at the transcriptional level and was dependent on reactive oxygen species and IL-1R signaling; it was abrogated with an IL-1R antagonist or with IL-1-neutralizing Abs, whereas treatment with either rIL-1alpha or IL-1beta induced IL-23 secretion. Dendritic cells treated with LPS and 3-methyladenine secreted enhanced levels of both IL-1beta and IL-23, and supernatants from these cells stimulated the innate secretion of IL-17, IFN-gamma, and IL-22 by gammadelta T cells. These data demonstrate that autophagy has a potentially pivotal role to play in the induction and regulation of inflammatory responses by innate immune cells, largely driven by IL-1 and its consequential effects on IL-23 secretion.
Original languageEnglish
Pages (from-to)4144 - 4153
Number of pages10
JournalJournal of Immunology
Issue number8
Publication statusPublished - 2012

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