RESUMO
Interleukin (IL)-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-deficient mice and found that they suffer from significantly higher airway hyperreactivity upon airway challenge. IL-22-deficiency led to increased eosinophil infiltration lymphocyte invasion and production of CCL17 (TARC), IL-5 and IL-13 in the lung. Mice treated with IL-22 before antigen challenge displayed reduced expression of CCL17 and IL-13 and significant amelioration of airway constriction and inflammation. We conclude that innate IL-22 limits airway inflammation, tissue damage and clinical decline in allergic lung disease.
Assuntos
Imunidade Inata/imunologia , Inflamação/complicações , Inflamação/imunologia , Interleucinas/biossíntese , Linfócitos/imunologia , Hipersensibilidade Respiratória/complicações , Hipersensibilidade Respiratória/imunologia , Alérgenos/imunologia , Animais , Biomarcadores/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Imunidade Inata/efeitos dos fármacos , Imunização , Imunoglobulinas/sangue , Inflamação/sangue , Inflamação/patologia , Interleucina-13/farmacologia , Interleucinas/administração & dosagem , Interleucinas/deficiência , Interleucinas/metabolismo , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Linfócitos/efeitos dos fármacos , Camundongos , Fosforilação/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Hipersensibilidade Respiratória/sangue , Fator de Transcrição STAT3/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/farmacologia , Interleucina 22RESUMO
B-cell activating factor (BAFF), a member of the TNF family, is a potent cytokine with stimulatory effects on B and T cells. To evaluate the potential of transient overexpression of BAFF to enhance vaccine immunogenicity, a replication-deficient adenovirus expressing full-length murine BAFF (AdBAFF) was tested in a mouse vaccine model against Pseudomonas aeruginosa. When coadministered with heat-killed P. aeruginosa, AdBAFF mediated a significant increase in anti-P. aeruginosa-specific serum and lung mucosal antibodies and resulted in improved protection against a lethal respiratory challenge with P. aeruginosa. This effect was independent of the site of administration of AdBAFF and was observed both when AdBAFF was given simultaneously with heat-killed P. aeruginosa as well as when AdBAFF was administered 4 weeks after immunization with heat-killed P. aeruginosa. These data demonstrate that a temporal increase in systemic BAFF levels is able to augment a P. aeruginosa-specific immune response upon immunization with heat-killed P. aeruginosa, suggesting that the immune-stimulatory effects of BAFF may be exploited as a molecular adjuvant for genetic vaccines.
