IL-21 Alleviates Allergic Asthma In DOCK8-Knockout Mice

Objective: To induce allergic asthma in DOCK8 knockout mice with low-dose OVA and treat those with recombinant mouse IL-21(rmIL-21)administration.To study the relationship between high level of Ig E and IL-21 through detecting the expiratory resistance,airway inflammation,serum IgE level and percentage IgE+ B cell in blood and spleen.Methods: OVA-induced allergic asthma was elicited by i.p.sensitization with 5 ug chicken ovalbumin(OVA)emulsified in 200 ul Imject Alum on day 0,followed by two oropharyngeal aspiration challenges with 1.5% OVA dissolved in 50 ul PBS on day 14 and 21.Control mice received only PBS.Mice were harvested 72 h after the second challenge.This exposure method referring to previous study was modified.Some groups of mice were administered 20 ng of recombinant mouse(rmIL-21)into the nostrils daily on days 15-17,whereas other groups of mice were not treated with the cytokine(WT-OVA or KO-OVA).As a negative control,groups of mice received neither sensitization nor challenge treatment(WT-con or KO-con).Total cell and eosinophils count in BALF,airway inflammattion,expiratory resistance,serum IgE level and percentage of IgE+ B cell in blood and spleen were detected.Results: As compared to that in WT mice,remarkable airway hyperresponsiveness was observed in KO mice.Increased inflammatory cells and eosinophils infiltrated in airway lumen in KO mice especially around bronchi.KO mice showed higher levels of serum Ig E and OVA-specific IgE and significantly elevated IgE-producing B cells in blood and in spleen.Surprisingly,nasal administration with rmIL-21 significantly reduced the airway hyperresponsiveness,inflammatory infiltration,as well as the serum IgE and IgE-producing B cells.Conclusion: DOCK8-knockout mice are susceptible to low-dose OVA induced allergic airway inflammation and airway hyperresponsiveness.Supplementary nasal administration of rmIL-21 alleviates allergic asthma in this mouse model.