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. 2022 Aug 16;20:369. doi: 10.1186/s12967-022-03570-w

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — IL-33 intracellular pathways. (1) IL-33 is mainly produced by endothelial cells, astrocytes, and oligodendrocytes. Its receptor complex ST2L/IL-1RAcP is constitutively expressed by microglia, astrocytes, and neurons in the hippocampus, which is associated with cognitive function. (2) IL-33 binds to the cell surface receptor complex ST2L/IL-1RAcP and induces MyD88 recruitment to the complex. (3) sST2 as an inducible receptor competes with ST2L to bind IL-33 and inhibits IL-33/ST2L signaling pathway-related effects. (4) Receptor-associated MyD88 facilitates the activation of IRAK1 and IRAK4 with TRAF6 recruitment. IRAKs induce the activation of IκB-α and IKK resulting in NF-κB activation. (5) Activated MyD88 also induces the phosphorylation of kinases ERK, and p38, along with IRAKs-induced JNK resulting in AP-1 activation. (6) NF-κB and AP-1 induce the production of the Th2-associated cytokines, including IL-4, IL-5, and IL-13