Year: 2020
Type: article
Abstract: 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-γ) orchestrates early inflammatory events, enhancing immune-mediated damage. The current study investigated IFN-γ during resolution in several experimental models of ALI. The absence of IFN-γ resulted in altered kinetics of lymphocyte and macrophage responses, suggesting that IFN-γ present in this microenvironment is influential in ALI resolution. Genetic deficiency of IFN-γ or administering neutralizing IFN-γ antibodies accelerated the pace of resolution. Neutralizing IFN-γ 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-γ concentrations affect immune cell kinetics and the rate of resolution. These findings suggest that therapies that spatially or temporally control IFN-γ 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.
Source: Physiological Reports
DOI: 10.14814/phy2.14368
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,600
Awards: Defining the Role of Regulatory T Cell-Derived MMP12 in Acute Lung Injury Resolution, G2164003581, Macrophage and monocyte TBK1 function in host defense against influenza, Trafficking and function of macrophage subpopulations within the lung microenvironment during pneumonia, Rho-mediated Signaling in Lung Endothelial Cells Induced by Neutrophil Adhesion, Regulatory T Cells Promote Alveolar Epithelial Repair, Application of Omics in Lung Disease, G8808056608
OpenAlex ID: W3006345366