IL-21 promotes the pathologic immune response to pneumovirus infection.

Abstract

IL-21 is a cytokine with pleiotropic actions, promoting terminal differentiation of B cells, increased Ig production, and the development of Th17 and T follicular helper cells. IL-21 is also implicated in the development of autoimmune disease and has antitumor activity. In this study, we investigated the role of IL-21 in host defense to pneumonia virus of mice (PVM), which initiates an infection in mice resembling that of respiratory syncytial virus disease in humans. We found that PVM-infected mice expressed IL-21 in lung CD4(+) T cells. Following infection, Il21r(-/-) mice exhibited less lung infiltration by neutrophils than did wild-type (WT) mice and correspondingly had lower levels of the chemokine CXCL1 in bronchoalveolar lavage fluid and lung parenchyma. CD8(+), CD4(+), and γδ T cell numbers were also lower in the lungs of PVM-infected Il21r(-/-) mice than in infected WT mice, with normal Th17 cytokines but diminished IL-6 production in PVM-infected Il21r(-/-) mice. Strikingly, Il21r(-/-) mice had enhanced survival following PVM infection, and moreover, treatment of WT mice with soluble IL-21R-Fc fusion protein enhanced their survival. These data reveal that IL-21 promotes the pathogenic inflammatory effect of PVM and indicate that manipulating IL-21 signaling may represent an immunomodulatory strategy for controlling PVM and potentially other respiratory virus infections.

• Authors: Rosanne Spolski, Lu Wang, Chi-Keung Wan, Cynthia A Bonville, Joseph B Domachowske, Hyoung-Pyo Kim, Zuxi Yu, Warren J Leonard
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 4 Pg. 1924-32 (Feb 15 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22238461 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL1
• Interleukin-6
• Interleukins
• Receptors, Interleukin-21
• interleukin-21

Topics

• Animals
• Bronchoalveolar Lavage Fluid (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Chemokine CXCL1 (biosynthesis, immunology)
• Interleukin-6 (biosynthesis, deficiency)
• Interleukins (biosynthesis, immunology, metabolism)
• Lung (immunology, pathology, virology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Murine pneumonia virus (immunology, pathogenicity)
• Pneumovirus Infections (immunology, pathology)
• Receptors, Interleukin-21 (immunology)
• Th17 Cells (immunology)