title: Endogenous IL-21 regulates pathogenic mucosal CD4 T-cell responses during enhanced RSV disease in mice.
abstract: A role for interleukin-21 (IL-21) has recently been found in several diseases, but contribution to mucosal defences has not been described. In BALB/c mice infected with respiratory syncytial virus (RSV), IL-21 depletion had little effect in primary infection. However, depletion of mice during priming with recombinant vaccinia expressing RSV G protein (which primes RSV-specific T helper type 2 cells and causes lung eosinophilia during RSV infection) further exacerbated pathology during RSV challenge, with reduced viral clearance and impaired virus-specific serum antibody responses. This enhancement was accompanied by lymphocyte, neutrophil, and antigen-presenting cell recruitment to the lungs, with increased bronchoalveolar lavage interferon-γ and IL-17 levels. Adoptive transfer of splenic CD4 T cells from depleted mice into naive recipients replicated these effects, indicating that IL-21 mediates its effects via CD4 T cells. Endogenous IL-21, therefore, has potent and specific effects on mucosal antiviral responses, assisting viral clearance, regulating pulmonary T- and B-cell responses, and inhibiting IL-17 production.
authors.affiliation: Section of Respiratory Infection, Faculty of Medicine, Centre for Respiratory Infections, National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Dodd
authors.forename: D
authors.initials: D
authors.lastname: Clark
authors.forename: R
authors.initials: R
authors.lastname: Muir
authors.forename: C
authors.initials: C
authors.lastname: Korpis
authors.forename: P J M
authors.initials: PJ
authors.lastname: Openshaw
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D007378:Interleukins; D007371:Interferon-gamma; D000098546:Interleukin-21