Inflammatory impact of IFN-7 in CD8+ T cell-mediated lung injury is mediated by both Statl-dependent and -independent pathways

摘要

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 nonviral murine model in which alveolar epithelial cells express an influenza antigen and injury is initiated by adoptive transfer of influenza-specific CD8+ T cells. We report that IFN-7 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-7 enhanced lung epithelial cell expression of chemokines and the subsequent recruitment of inflammatory cells into the airways. Surprisingly, Statl 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-7 production by these cells. Loss of Statl resulted in sustained activation of Stat3 signaling, dysregu-lated chemokine expression, and increased infiltration of the airways by inflammatory cells. Taken together, these data identify important roles for IFN-7 signaling and Statl-independent IFN-7 signaling in regulating CD8+ T cell-mediated acute lung injury. This is the first study to demonstrate an anti-inflammatory effect of Statl on CD8+ T cell-mediated lung immunopathology without the complication of differences in viral load.