Details

Autor(en) / Beteiligte

• Muallem, Gaia
• Wagage, Sagie
• Sun, Yan
• DeLong, Jonathan H
• Valenzuela, Alex
• Christian, David A
• Harms Pritchard, Gretchen
• Fang, Qun
• Buza, Elizabeth L
• Jain, Deepika
• Elloso, M Merle
• López, Carolina B
• Hunter, Christopher A
• Heise, Mark T.

Titel

IL-27 Limits Type 2 Immunopathology Following Parainfluenza Virus Infection

Ist Teil von

• PLoS pathogens, 2017-01, Vol.13 (1), p.e1006173-e1006173

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2017

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Respiratory paramyxoviruses are important causes of morbidity and mortality, particularly of infants and the elderly. In humans, a T helper (Th)2-biased immune response to these infections is associated with increased disease severity; however, little is known about the endogenous regulators of these responses that may be manipulated to ameliorate pathology. IL-27, a cytokine that regulates Th2 responses, is produced in the lungs during parainfluenza infection, but its role in disease pathogenesis is unknown. To determine whether IL-27 limits the development of pathogenic Th2 responses during paramyxovirus infection, IL-27-deficient or control mice were infected with the murine parainfluenza virus Sendai virus (SeV). Infected IL-27-deficient mice experienced increased weight loss, more severe lung lesions, and decreased survival compared to controls. IL-27 deficiency led to increased pulmonary eosinophils, alternatively activated macrophages (AAMs), and the emergence of Th2 responses. In control mice, IL-27 induced a population of IFN-γ+/IL-10+ CD4+ T cells that was replaced by IFN-γ+/IL-17+ and IFN-γ+/IL-13+ CD4+ T cells in IL-27-deficient mice. CD4+ T cell depletion in IL-27-deficient mice attenuated weight loss and decreased AAMs. Elimination of STAT6 signaling in IL-27-deficient mice reduced Th2 responses and decreased disease severity. These data indicate that endogenous IL-27 limits pathology during parainfluenza virus infection by regulating the quality of CD4+ T cell responses and therefore may have therapeutic potential in paramyxovirus infections.