RGD Reference Report - IL-21 promotes the pathologic immune response to pneumovirus infection. - Rat Genome Database

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

Authors: Spolski, R  Wang, L  Wan, CK  Bonville, CA  Domachowske, JB  Kim, HP  Yu, Z  Leonard, WJ 
Citation: Spolski R, etal., J Immunol. 2012 Feb 15;188(4):1924-32. Epub 2012 Jan 11.
RGD ID: 6892925
Pubmed: PMID:22238461   (View Abstract at PubMed)
PMCID: PMC3277853   (View Article at PubMed Central)
DOI: DOI:10.4049/jimmunol.1100767   (Journal Full-text)

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 gammadelta 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Pneumovirus Infections  ISOIl21 (Mus musculus)6892925; 6892925mRNA:increased expression:lung (mouse)RGD 
Pneumovirus Infections  ISORDG:13126886892925; 6892925 RGD 
Pneumovirus Infections  IEP 6892925mRNA:increased expression:lung (mouse)RGD 
Pneumovirus Infections  IMP 6892925 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il21  (interleukin 21)
Il21r  (interleukin 21 receptor)

Genes (Mus musculus)
Il21  (interleukin 21)
Il21r  (interleukin 21 receptor)

Genes (Homo sapiens)
IL21  (interleukin 21)
IL21R  (interleukin 21 receptor)


Additional Information