| First Author | Liu FD | Year | 2014 |
| Journal | PLoS Pathog | Volume | 10 |
| Issue | 5 | Pages | e1004110 |
| PubMed ID | 24809349 | Mgi Jnum | J:246141 |
| Mgi Id | MGI:5918859 | Doi | 10.1371/journal.ppat.1004110 |
| Citation | Liu FD, et al. (2014) Timed action of IL-27 protects from immunopathology while preserving defense in influenza. PLoS Pathog 10(5):e1004110 |
| abstractText | Infection with influenza virus can result in massive pulmonary infiltration and potentially fatal immunopathology. Understanding the endogenous mechanisms that control immunopathology could provide a key to novel adjunct therapies for this disease. Here we show that the cytokine IL-27 plays a crucial role in protection from exaggerated inflammation during influenza virus infection. Using Il-27ra-/- mice, IL-27 was found to limit immunopathology, neutrophil accumulation, and dampened TH1 or TH17 responses via IL-10-dependent and -independent pathways. Accordingly, the absence of IL-27 signals resulted in a more severe disease course and in diminished survival without impacting viral loads. Consistent with the delayed expression of endogenous Il-27p28 during influenza, systemic treatment with recombinant IL-27 starting at the peak of virus load resulted in a major amelioration of lung pathology, strongly reduced leukocyte infiltration and improved survival without affecting viral clearance. In contrast, early application of IL-27 impaired virus clearance and worsened disease. These findings demonstrate the importance of IL-27 for the physiological control of immunopathology and the potential value of well-timed IL-27 application to treat life-threatening inflammation during lung infection. |
