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Am J Physiol Lung Cell Mol Physiol. 2015 Jan 23:ajplung.00360.2014. doi: 10.1152/ajplung.00360.2014. [Epub ahead of print]
Inflammatory impact of IFN-γ in CD8+ T-cell-mediated lung injury is mediated by both Stat1-dependent and -independent pathways.
Ramana CV1, DeBerge MP1, Kumar A2, Alia CS3, Durbin JE4, Enelow RI5.
Author information
Abstract
Influenza infection results in considerable pulmonary pathology, a significant component of which is mediated by CD8+ T cell effector functions. To isolate the specific contribution of CD8+ T cells to lung immunopathology, we utilized a non-viral murine model in which alveolar epithelial cells express an influenza antigen and injury is initiated by adoptively transferring influenza-specific CD8+ T cells. Here, we report that IFN-γ production by adoptively transferred influenza-specific CD8+ T cells is a significant contributor to acute lung injury following influenza antigen recognition, in isolation from its impact on viral clearance. CD8+ T cell production of IFN-γ enhanced lung epithelial cell expression of chemokines, and the subsequent recruitment of inflammatory cells into the airways. Surprisingly, Stat1-deficiency in the adoptive-transfer recipients exacerbated the lung injury that was mediated by the transferred influenza-specific CD8+ T cells but was still dependent on IFN-γ production by these cells. Loss of Stat1 resulted in sustained activation of Stat3 signaling, dysregulated chemokine expression, and increased infiltration of the airways by inflammatory cells. Taken together, these data identify important roles for both IFN-γ signaling and Stat1-independent IFN-γ signaling in regulating CD8+ T cell-mediated acute lung injury, and is the first study to demonstrate an anti-inflammatory effect of Stat1 in CD8+ T cell-mediated lung immunopathology without the complication of differences in viral load.
Copyright ? 2014, American Journal of Physiology - Lung Cellular and Molecular Physiology.
KEYWORDS:
Acute lung injury; CD8 T cell; IFN-γ; Stat1; immunopathology
PMID: 25617378 [PubMed - as supplied by publisher]
Inflammatory impact of IFN-γ in CD8+ T-cell-mediated lung injury is mediated by both Stat1-dependent and -independent pathways.
Ramana CV1, DeBerge MP1, Kumar A2, Alia CS3, Durbin JE4, Enelow RI5.
Author information
Abstract
Influenza infection results in considerable pulmonary pathology, a significant component of which is mediated by CD8+ T cell effector functions. To isolate the specific contribution of CD8+ T cells to lung immunopathology, we utilized a non-viral murine model in which alveolar epithelial cells express an influenza antigen and injury is initiated by adoptively transferring influenza-specific CD8+ T cells. Here, we report that IFN-γ production by adoptively transferred influenza-specific CD8+ T cells is a significant contributor to acute lung injury following influenza antigen recognition, in isolation from its impact on viral clearance. CD8+ T cell production of IFN-γ enhanced lung epithelial cell expression of chemokines, and the subsequent recruitment of inflammatory cells into the airways. Surprisingly, Stat1-deficiency in the adoptive-transfer recipients exacerbated the lung injury that was mediated by the transferred influenza-specific CD8+ T cells but was still dependent on IFN-γ production by these cells. Loss of Stat1 resulted in sustained activation of Stat3 signaling, dysregulated chemokine expression, and increased infiltration of the airways by inflammatory cells. Taken together, these data identify important roles for both IFN-γ signaling and Stat1-independent IFN-γ signaling in regulating CD8+ T cell-mediated acute lung injury, and is the first study to demonstrate an anti-inflammatory effect of Stat1 in CD8+ T cell-mediated lung immunopathology without the complication of differences in viral load.
Copyright ? 2014, American Journal of Physiology - Lung Cellular and Molecular Physiology.
KEYWORDS:
Acute lung injury; CD8 T cell; IFN-γ; Stat1; immunopathology
PMID: 25617378 [PubMed - as supplied by publisher]