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IL-21 promotes the pathologic immune response to pneumovirus infection

Authors
 Rosanne Spolski  ;  Lu Wang  ;  Chi-Keung Wan  ;  Cynthia A. Bonville  ;  Joseph B. Domachowske  ;  Hyoung-Pyo Kim  ;  Zuxi Yu  ;  Warren J. Leonard 
Citation
 JOURNAL OF IMMUNOLOGY, Vol.188(4) : 1924-1932, 2012 
Journal Title
JOURNAL OF IMMUNOLOGY
ISSN
 0022-1767 
Issue Date
2012
MeSH
Animals ; Bronchoalveolar Lavage Fluid/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Chemokine CXCL1/biosynthesis ; Chemokine CXCL1/immunology ; Interleukin-6/biosynthesis ; Interleukin-6/deficiency ; Interleukins/biosynthesis ; Interleukins/immunology* ; Interleukins/metabolism ; Lung/immunology ; Lung/pathology ; Lung/virology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Murine pneumonia virus/immunology* ; Murine pneumonia virus/pathogenicity ; Pneumovirus Infections/immunology* ; Pneumovirus Infections/pathology* ; Receptors, Interleukin-21/immunology ; Th17 Cells/immunology
Keywords
Animals ; Bronchoalveolar Lavage Fluid/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Chemokine CXCL1/biosynthesis ; Chemokine CXCL1/immunology ; Interleukin-6/biosynthesis ; Interleukin-6/deficiency ; Interleukins/biosynthesis ; Interleukins/immunology* ; Interleukins/metabolism ; Lung/immunology ; Lung/pathology ; Lung/virology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Murine pneumonia virus/immunology* ; Murine pneumonia virus/pathogenicity ; Pneumovirus Infections/immunology* ; Pneumovirus Infections/pathology* ; Receptors, Interleukin-21/immunology ; Th17 Cells/immunology
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.
DOI
22238461
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90850
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