| First Author | Mock JR | Year | 2020 |
| Journal | Physiol Rep | Volume | 8 |
| Issue | 3 | Pages | e14368 |
| PubMed ID | 32061190 | Mgi Jnum | J:301189 |
| Mgi Id | MGI:6502957 | Doi | 10.14814/phy2.14368 |
| Citation | Mock JR, et al. (2020) Effects of IFN-gamma on immune cell kinetics during the resolution of acute lung injury. Physiol Rep 8(3):e14368 |
| abstractText | The immunologic responses that occur early in the acute respiratory distress syndrome (ARDS) elicit immune-mediated damage. The mechanisms underlying the resolution of ARDS, particularly the role of signaling molecules in regulating immune cell kinetics, remain important questions. Th1-mediated responses can contribute to the pathogenesis of acute lung injury (ALI). Interferon-gamma (IFN-gamma) orchestrates early inflammatory events, enhancing immune-mediated damage. The current study investigated IFN-gamma during resolution in several experimental models of ALI. The absence of IFN-gamma resulted in altered kinetics of lymphocyte and macrophage responses, suggesting that IFN-gamma present in this microenvironment is influential in ALI resolution. Genetic deficiency of IFN-gamma or administering neutralizing IFN-gamma antibodies accelerated the pace of resolution. Neutralizing IFN-gamma decreased the numbers of interstitial and inflammatory macrophages and increased alveolar macrophage numbers during resolution. Our results underline the complexity of lung injury resolution and provide insight into the effects through which altered IFN-gamma concentrations affect immune cell kinetics and the rate of resolution. These findings suggest that therapies that spatially or temporally control IFN-gamma signaling may promote ALI resolution. Identifying and elucidating the mechanisms critical to ALI resolution will allow the development of therapeutic approaches to minimize collateral tissue damage without adversely altering the response to injury. |
