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

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

Scientific reports (2020-02-28)
Tsvetana Petrova, Jelena Pesic, Katerina Pardali, Matthias Gaestel, J Simon C Arthur
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 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Rapamycin, ≥95% (HPLC), powder
Sigma-Aldrich
Human Serum, Heat Inactivated (from male AB clotted whole blood), USA origin, sterile-filtered