p38 MAPK signalling regulates cytokine production in IL-33 stimulated Type 2 Innate Lymphoid cells
(2020) In Scientific Reports 10(1). p.3479-3479- 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 IL-13 (two... (More)
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 IL-13 (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 IL-13 production, which would be consistent with a model in which MK2/3 regulate IL-6 and IL-13 via mTORC1 activation in ILC2s.
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- author
- Petrova, Tsvetana ; Pesic, Jelena LU ; Pardali, Katerina ; Gaestel, Matthias and Arthur, J Simon C
- publishing date
- 2020-02-26
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Cells, Cultured, Cytokines/metabolism, Down-Regulation/drug effects, Humans, Interleukin-13/metabolism, Interleukin-33/pharmacology, Interleukin-6/metabolism, Intracellular Signaling Peptides and Proteins/antagonists & inhibitors, Lymphocytes/cytology, MAP Kinase Signaling System/drug effects, Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphorylation/drug effects, Protein Kinase Inhibitors/pharmacology, Protein-Serine-Threonine Kinases/antagonists & inhibitors, Sirolimus/pharmacology, p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
- in
- Scientific Reports
- volume
- 10
- issue
- 1
- pages
- 3479 - 3479
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:32103032
- scopus:85080052256
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-020-60089-0
- language
- English
- LU publication?
- no
- id
- b9adfaed-101d-45a1-918d-956c9e6e54d6
- date added to LUP
- 2021-04-15 09:53:36
- date last changed
- 2024-06-16 12:26:38
@article{b9adfaed-101d-45a1-918d-956c9e6e54d6, abstract = {{<p>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 IL-13 (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 IL-13 production, which would be consistent with a model in which MK2/3 regulate IL-6 and IL-13 via mTORC1 activation in ILC2s.</p>}}, author = {{Petrova, Tsvetana and Pesic, Jelena and Pardali, Katerina and Gaestel, Matthias and Arthur, J Simon C}}, issn = {{2045-2322}}, keywords = {{Animals; Cells, Cultured; Cytokines/metabolism; Down-Regulation/drug effects; Humans; Interleukin-13/metabolism; Interleukin-33/pharmacology; Interleukin-6/metabolism; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors; Lymphocytes/cytology; MAP Kinase Signaling System/drug effects; Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphorylation/drug effects; Protein Kinase Inhibitors/pharmacology; Protein-Serine-Threonine Kinases/antagonists & inhibitors; Sirolimus/pharmacology; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors}}, language = {{eng}}, month = {{02}}, number = {{1}}, pages = {{3479--3479}}, publisher = {{Nature Publishing Group}}, series = {{Scientific Reports}}, title = {{p38 MAPK signalling regulates cytokine production in IL-33 stimulated Type 2 Innate Lymphoid cells}}, url = {{http://dx.doi.org/10.1038/s41598-020-60089-0}}, doi = {{10.1038/s41598-020-60089-0}}, volume = {{10}}, year = {{2020}}, }