MK2/3 Are Pivotal for IL-33–Induced and Mast Cell–Dependent Leukocyte Recruitment and the Resulting Skin Inflammation

  • Drube S
  • Kraft F
  • Dudeck J
  • et al.
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Abstract

The IL-1R family member IL-33R mediates Fcε-receptor-I (FcεRI)-independent activation of mast cells leading to NF-κB activation and consequently the production of cytokines. IL-33 also induces the activation of MAPKs, such as p38. We aimed to define the relevance of the p38-targets, the MAPK-activated protein kinases 2 and 3 (MK2 and MK3) in IL-33-induced signaling and the resulting mast cell effector functions in vitro and in vivo. We demonstrate that the IL-33-induced IL-6 and IL-13 production strongly depends on the MK2/3-mediated activation of ERK1/2 and PI3K signaling. Furthermore, in the presence of the stem cell factors, IL-33 did induce an MK2/3-, ERK1/2- and PI3K-dependent production of TNF-α. In vivo, the loss of MK2/3 in mast cells decreased the IL-33-induced leukocyte recruitment and the resulting skin inflammation. Therefore, the MK2/3-dependent signaling in mast cells is essential to mediate IL-33-induced inflammatory responses. Thus, MK2/3 are potential therapeutic targets for suppression of IL-33-induced inflammation skin diseases such as psoriasis.

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APA

Drube, S., Kraft, F., Dudeck, J., Müller, A.-L., Weber, F., Göpfert, C., … Kamradt, T. (2016). MK2/3 Are Pivotal for IL-33–Induced and Mast Cell–Dependent Leukocyte Recruitment and the Resulting Skin Inflammation. The Journal of Immunology, 197(9), 3662–3668. https://doi.org/10.4049/jimmunol.1600658

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