{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang Z"],"funding":["NHLBI NIH HHS","National Institutes of Health"],"pagination":["338-352"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10913761"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["194(3)"],"pubmed_abstract":["The high mortality rates of acute lung injury and acute respiratory distress syndrome challenge the field to identify biomarkers and factors that can be exploited for therapeutic approaches. IL-22 is a cytokine that has antibacterial and reparative properties in the lung. However, it also can exacerbate inflammation and requires tight control by the extracellular inhibitory protein known as IL-22 binding protein (IL-22BP) (Il22ra2). This study showed the necessity of IL-22BP in controlling and preventing acute lung injury using IL-22BP knockout mice (Il22ra2<sup>-/-</sup>) in the bleomycin model of acute lung injury/acute respiratory distress syndrome. Il22ra2<sup>-/-</sup> mice had greater sensitivity (weight loss and death) and pulmonary inflammation in the acute phase (first 7 days) of the injury compared with wild-type C57Bl/6 controls. The inflammation was driven by excess IL-22 production, inducing the influx of pathogenic IL-17A<sup>+</sup> γδ T cells to the lung. Interestingly, this inflammation was initiated in part by the noncanonical IL-22 signaling to macrophages, which express the IL-22 receptor (Il22ra1) in vivo after bleomycin challenge. This study further showed that IL-22 receptor alpha-1<sup>+</sup> macrophages can be stimulated by IL-22 to produce a number of IL-17-inducing cytokines such as IL-1β, IL-6, and transforming growth factor-β1. Together, the results suggest that IL-22BP prevents IL-22 signaling to macrophages and reduces bleomycin-mediated lung injury."],"journal":["The American journal of pathology"],"pubmed_title":["IL-22 Binding Protein Controls IL-22-Driven Bleomycin-Induced Lung Injury."],"pmcid":["PMC10913761"],"funding_grant_id":["RO1HL122760","R01 HL122760"],"pubmed_authors":["Jones M","Frydman JA","Galeas-Pena M","Zhang Z","Allen MJ","Chakawa MB","Pociask D"],"additional_accession":[]},"is_claimable":false,"name":"IL-22 Binding Protein Controls IL-22-Driven Bleomycin-Induced Lung Injury.","description":"The high mortality rates of acute lung injury and acute respiratory distress syndrome challenge the field to identify biomarkers and factors that can be exploited for therapeutic approaches. IL-22 is a cytokine that has antibacterial and reparative properties in the lung. However, it also can exacerbate inflammation and requires tight control by the extracellular inhibitory protein known as IL-22 binding protein (IL-22BP) (Il22ra2). This study showed the necessity of IL-22BP in controlling and preventing acute lung injury using IL-22BP knockout mice (Il22ra2<sup>-/-</sup>) in the bleomycin model of acute lung injury/acute respiratory distress syndrome. Il22ra2<sup>-/-</sup> mice had greater sensitivity (weight loss and death) and pulmonary inflammation in the acute phase (first 7 days) of the injury compared with wild-type C57Bl/6 controls. The inflammation was driven by excess IL-22 production, inducing the influx of pathogenic IL-17A<sup>+</sup> γδ T cells to the lung. Interestingly, this inflammation was initiated in part by the noncanonical IL-22 signaling to macrophages, which express the IL-22 receptor (Il22ra1) in vivo after bleomycin challenge. This study further showed that IL-22 receptor alpha-1<sup>+</sup> macrophages can be stimulated by IL-22 to produce a number of IL-17-inducing cytokines such as IL-1β, IL-6, and transforming growth factor-β1. Together, the results suggest that IL-22BP prevents IL-22 signaling to macrophages and reduces bleomycin-mediated lung injury.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-03T23:36:22.477Z","creation":"2025-04-03T23:36:22.477Z"},"accession":"S-EPMC10913761","cross_references":{"pubmed":["38101567"],"doi":["10.1016/j.ajpath.2023.11.011"]}}