{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen W"],"funding":["Intramural NIH HHS"],"pagination":["1021-1030"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11345751"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(7)"],"pubmed_abstract":["Interleukin-33 (IL-33), an epithelial cell-derived cytokine that responds rapidly to environmental insult, has a critical role in initiating airway inflammatory diseases. However, the molecular mechanism underlying IL-33 secretion following allergen exposure is not clear. Here, we found that two cell events were fundamental for IL-33 secretion after exposure to allergens. First, stress granule assembly activated by allergens licensed the nuclear-cytoplasmic transport of IL-33, but not the secretion of IL-33. Second, a neo-form murine amino-terminal p40 fragment gasdermin D (Gsdmd), whose generation was independent of inflammatory caspase-1 and caspase-11, dominated cytosolic secretion of IL-33 by forming pores in the cell membrane. Either the blockade of stress granule assembly or the abolishment of p40 production through amino acid mutation of residues 309-313 (ELRQQ) could efficiently prevent the release of IL-33 in murine epithelial cells. Our findings indicated that targeting stress granule disassembly and Gsdmd fragmentation could reduce IL-33-dependent allergic airway inflammation."],"journal":["Nature immunology"],"pubmed_title":["Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion."],"pmcid":["PMC11345751"],"funding_grant_id":["ZIA AI001169"],"pubmed_authors":["Zhang D","Long G","Ma L","Lu X","Zhang J","Sun B","Jiang H","Fu Y","Wu B","Wu D","Zhang R","Iv H","Chen W","Chen S","Fan W","Chen M","Lv D","Li X","Huang Y","Zhu J","Zhong S","Zhang Y","Zhu L","Yan C","Ling Z","Zhu S"],"additional_accession":[]},"is_claimable":false,"name":"Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion.","description":"Interleukin-33 (IL-33), an epithelial cell-derived cytokine that responds rapidly to environmental insult, has a critical role in initiating airway inflammatory diseases. However, the molecular mechanism underlying IL-33 secretion following allergen exposure is not clear. Here, we found that two cell events were fundamental for IL-33 secretion after exposure to allergens. First, stress granule assembly activated by allergens licensed the nuclear-cytoplasmic transport of IL-33, but not the secretion of IL-33. Second, a neo-form murine amino-terminal p40 fragment gasdermin D (Gsdmd), whose generation was independent of inflammatory caspase-1 and caspase-11, dominated cytosolic secretion of IL-33 by forming pores in the cell membrane. Either the blockade of stress granule assembly or the abolishment of p40 production through amino acid mutation of residues 309-313 (ELRQQ) could efficiently prevent the release of IL-33 in murine epithelial cells. Our findings indicated that targeting stress granule disassembly and Gsdmd fragmentation could reduce IL-33-dependent allergic airway inflammation.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2025-04-21T15:26:28.337Z","creation":"2025-04-21T15:26:28.337Z"},"accession":"S-EPMC11345751","cross_references":{"pubmed":["35794369"],"doi":["10.1038/s41590-022-01255-6"]}}