| First Author | Zhang Z | Year | 2024 |
| Journal | Am J Pathol | Volume | 194 |
| Issue | 3 | Pages | 338-352 |
| PubMed ID | 38101567 | Mgi Jnum | J:346205 |
| Mgi Id | MGI:7611389 | Doi | 10.1016/j.ajpath.2023.11.011 |
| Citation | Zhang Z, et al. (2024) IL-22 Binding Protein Controls IL-22-Driven Bleomycin-Induced Lung Injury. Am J Pathol 194(3):338-352 |
| abstractText | 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(-/-)) in the bleomycin model of acute lung injury/acute respiratory distress syndrome. Il22ra2(-/-) 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(+) gammadelta 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(+) macrophages can be stimulated by IL-22 to produce a number of IL-17-inducing cytokines such as IL-1beta, IL-6, and transforming growth factor-beta1. Together, the results suggest that IL-22BP prevents IL-22 signaling to macrophages and reduces bleomycin-mediated lung injury. |
