IL-22 Is Produced by Innate Lymphoid Cells and Limits Inflammation in Allergic Airway Disease

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

Impfempfehlungen für Deutschland

Hintergrund: Impfungen stellen eine effektive Maßnahme zum Schutz vor Infektionskrankheiten dar. In Deutschland werden Empfehlungen für Impfungen, die populationsbezogen das Auftreten und die Ausbreitung von Infektionen verhindern können, durch die Ständige Impfkommission (STIKO) am Robert Koch-Institut (RKI) auf Grundlage von infektionsepidemiologischen Erkenntnissen vorbereitet. Methoden: Selektive Literaturrecherche unter Berücksichtigung der aktuellen STIKO-Impfempfehlungen. Ergebnisse: Die Impfempfehlungen sind im jährlich aktualisierten Impfkalender dargestellt und umfassen ab der achten vollendeten Lebenswoche Impfungen gegen Diphtherie, Tetanus, Pertussis, Haemophilus influenzae Typ b, Hepatitis B, Poliomyelitis und Pneumokokken. Ab dem zweiten Lebensjahr folgen Impfungen gegen Masern, Mumps, Röteln, Varizellen und Meningokokken der Serogruppe C. Im Kindes- und Jugendalter werden Auffrischimpfungen und das Schließen von Impflücken empfohlen. Mädchen werden, nach der Empfehlung der STIKO, im Alter von 12 bis 17 Jahre gegen Humane Papillomviren geimpft. Bei Erwachsenen sollen regelmäßig die Impfungen gegen Tetanus, Diphtherie sowie einmalig gegen Pertussis aufgefrischt werden, und ab dem 60. Lebensjahr sollten Erwachsene gegen Pneumokokken und Influenza geimpft werden. Schlussfolgerungen: Mit den von der STIKO empfohlenen für alle Bürger kostenfreien Impfungen kann ein effektiver Infektionsschutz aufgebaut werden.Background: Vaccination is an effective means of preventing infectious diseases. In Germany, the Standing Vaccination Committee at the Robert Koch Institute (Ständige Impfkommission, STIKO) issues recommendations on vaccination to prevent the occurrence and spread of infectious diseases in the nation’s population. Methods: Selective literature review, including consideration of the current STIKO recommendations. Results: The annually updated vaccination calendar currently includes recommendations for vaccination against diphtheria, tetanus, pertussis, type b Haemophilus influenzae, hepatitis B, poliomyelitis, and pneumococci, beginning at the age of eight weeks. From the age of twelve months onward, children should be vaccinated against measles, mumps, rubella, varicella, and serogroup C meningococci. In later childhood and adolescence, booster vaccinations are recommended, in addition to the provision of any vaccinations that may have been missed. Girls aged 12 to 17 years should be vaccinated against human papilloma virus. Adults should have their tetanus and diphtheria vaccinations refreshed regularly, and their pertussis vaccination refreshed once; from age 60 onward, they should be vaccinated against pneumococci and influenza. Conclusions: The vaccinations recommended by the STIKO are available to all German citizens free of charge and provide effective protection against infectious disease

Expression of B-Cell Activating Factor Enhances Protective Immunity of a Vaccine against Pseudomonas aeruginosa▿

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

Naturally occurring short splice variant of CYLD positively regulates dendritic cell function

Deubiquitination of NF-kappa B members by CYLD is crucial in controlling the magnitude and nature of cell activation. The role of the naturally occurring CYLD splice variant in dendritic cell (DC) function was analyzed using CYLDex7/8 mice, which lack the full-length CYLD (flCYLD) transcript and overexpress the short splice variant (sCYLD). Bone marrow-derived DCs from CYLDex7/8 mice display a hyperactive phenotype in vitro and in vivo and have a defect in establishing tolerance with the use of DEC-205-mediated antigen targeting to resting DCs. The combination of sCYLD overexpression and lack of flCYLD in CYLDex7/8 DCs leads to enhanced NF-kappa B activity accompanied by an increased nuclear translocation of the I kappa B molecule Bcl-3, along with nuclear p50 and p65. This suggests that, in contrast to flCYLD, sCYLD is a positive regulator of NF-kappa B activity, and its overexpression induces a hyperactive phenotype in DCs. (Blood. 2009; 113: 5891-5895

Intracellular cytokine staining of mononuclear cells in the lung.

<p>Cells were isolated from either challenged only (c) or sensitized and challenged (s/c) <i>Il22</i> deficient and congenic wild-type controls (IL-22^+/+). Panel A shows a representative plot of intracellular IL-5 and IFN-γ staining. Panel B shows cell counts for IL-4 positive, IFN-γ negative (IL-4⁺IFN⁻), IL-5 positive, IFN-γ negative (IL-5⁺IFN⁻), IFN-γ positive, IL-5 negative (IFN⁺IL-5⁻) and IL-17A positive, IFN-γ negative (IL-17A⁺IFN⁻) cells. Each dot represent a single mouse. Data from 2 independent experiments are given. * p<0.05 compared to all other groups.</p

Analysis of cytokine production and surface markers of infiltrating mononuclear cells in the lungs.

<p>Panel A shows the expression of CD25 and CD44 among IL-22 producing cells. Panel B shows the IFN-γ and IL-17A production from sensitized and challenged mouse lungs. Panel C shows the expression of Rorgt. Rorc-eYFP mice were sensitized and challenged and the lung infiltrating mononuclear cells were analyzed for the expression of YFP.</p

Histology score and PAS-positive cells in airway epithelium.

<p>Peribronchial inflammation was graded by a semi-quantitative score (no inflammation = 0 to severe inflammation = 4). For each slide 5 randomly chosen areas were scored. Goblet cell metaplasia is expressed as number of PAS-positive cells per mm of basement membrane (BM). Mean values±SEM are given, n = 12 per group. N.D.: not detectable.</p><p>*p<0.05 compared to sens/chall PBS.</p