p38 MAPK signalling regulates cytokine production in IL-33 stimulated Type 2 Innate Lymphoid cells

Tsvetana Petrova, Jelena Pesic, Katerina Pardali, Matthias Gaestel, J. Simon C. Arthur (Lead / Corresponding author)

Research output: Contribution to journalArticle

1 Citation (Scopus)
33 Downloads (Pure)

Abstract

Type 2 Innate lymphoid cells (ILC2s) are implicated in helminth infections and asthma where they play a role in the production of Th2-type cytokines. ILC2s express the IL-33 receptor and are a major cell type thought to mediate the effects of this cytokine in vivo. To study the signalling pathways that mediate IL-33 induced cytokine production, a culture system was set up to obtain pure populations of ILC2s from mice. Inhibitors of the p38α/β and ERK1/2 MAPK pathways reduced the production of IL-5, IL-6, IL-9, IL-13 and GM-CSF by ILC2 in response to IL-33, with inhibition of p38 having the greatest effect. MK2 and 3 are kinases activated by p38α; MK2/3 inhibitors or knockout of MK2/3 in mice reduced the production of IL-6 and IL13 (two cytokines implicated in asthma) but not IL-5, IL-9 or GM-CSF in response to IL-33. MK2/3 inhibition also suppressed IL-6 and IL-13 production by human ILC2s. MK2/3 were required for maximal S6 phosphorylation, suggesting an input from the p38α-MK2/3 pathway to mTOR1 activation in ILC2s. The mTORC1 inhibitor rapamycin also reduced IL-6 and IL13 production, which would be consistent with a model in which MK2/3 regulate IL-6 and IL13 via mTORC1 activation in ILC2s.
Original languageEnglish
Article number3479
Pages (from-to)1-15
Number of pages15
JournalScientific Reports
Volume10
DOIs
Publication statusPublished - 26 Feb 2020

Keywords

  • Interleukins
  • Phosphorylation
  • Stress signalling

Fingerprint Dive into the research topics of 'p38 MAPK signalling regulates cytokine production in IL-33 stimulated Type 2 Innate Lymphoid cells'. Together they form a unique fingerprint.

  • Cite this