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

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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
Volume189
Issue number8
DOIs
Publication statusPublished - 2012

Cite this

Peral de Castro, Celia ; Jones, Sarah A ; Cheallaigh, Cliona Ni ; Hearnden, Claire A ; Williams, Laura K ; Winter, Jan ; Lavelle, Ed C ; Mills, Kingston H G ; Harris, James. / Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion. In: Journal of Immunology. 2012 ; Vol. 189, No. 8. pp. 4144 - 4153.
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title = "Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion",
abstract = "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.",
author = "{Peral de Castro}, Celia and Jones, {Sarah A} and Cheallaigh, {Cliona Ni} and Hearnden, {Claire A} and Williams, {Laura K} and Jan Winter and Lavelle, {Ed C} and Mills, {Kingston H G} and James Harris",
year = "2012",
doi = "10.4049/jimmunol.1201946",
language = "English",
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Peral de Castro, C, Jones, SA, Cheallaigh, CN, Hearnden, CA, Williams, LK, Winter, J, Lavelle, EC, Mills, KHG & Harris, J 2012, 'Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion' Journal of Immunology, vol. 189, no. 8, pp. 4144 - 4153. https://doi.org/10.4049/jimmunol.1201946

Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion. / Peral de Castro, Celia; Jones, Sarah A; Cheallaigh, Cliona Ni; Hearnden, Claire A; Williams, Laura K; Winter, Jan; Lavelle, Ed C; Mills, Kingston H G; Harris, James.

In: Journal of Immunology, Vol. 189, No. 8, 2012, p. 4144 - 4153.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion

AU - Peral de Castro, Celia

AU - Jones, Sarah A

AU - Cheallaigh, Cliona Ni

AU - Hearnden, Claire A

AU - Williams, Laura K

AU - Winter, Jan

AU - Lavelle, Ed C

AU - Mills, Kingston H G

AU - Harris, James

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AB - 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.

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