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. 2023 Dec 6;14:1304758. doi: 10.3389/fimmu.2023.1304758

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Copyright © 2023 Nouri, Schaunaman, Kraft, Li, Numata and Chu

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Proposed mechanisms by which Tollip regulates type 2 inflammation during influenza A virus (IAV) infection. Tollip deficiency enhances the release of ATP in lungs exposed to allergens and viruses. ATP binds to its receptor P2Y13 on epithelial cells, leading to IL-33 release. IL-33 binds to ST2L on different cell types, and results in type 2 cytokine release. Blocking ATP and IL-33 signaling by MRS2211 and sST2 attenuates excessive type 2 inflammation during IAV infection in Tollip deficient lungs. AT1; alveolar type I cell, AT2; alveolar type II cell. Created with BioRender.com. Tollip structure was extracted from protein data bank (www.rcsb.org).