The IL-15 / sIL-15Rα complex modulates immunity without effect on asthma features in mouse

Abstract

Background Interleukin 15 (IL-15) is a growth and modulating factor for B, T lymphocytes and natural killer cells (NK). Its action on innate and adaptive immunity is modulated by its alpha chain receptor (IL-15Rα). The IL-15/sIL-15Rα complex (IL-15Cx) increases the bioavailability and activity of the cytokine in vivo. IL-15Cx has been used in diseases to dampen IL-15 inflammation by the use of soluble IL-15Ralpha specificity. Here, we aim to evaluate the interest of IL-15Cx in a mouse model of asthma. Methods Using a mouse model of asthma consisting in percutaneous sensitization and intranasal challenge with total house dust mite extract, we evaluated the effect of IL-15Cx injected intraperitoneally four times after a first nasal challenge. Respiratory function was assessed by the technique of forced oscillations (Flexivent®). The effect on bronchial remodeling was evaluated by lung histology. The inflammatory status was analyzed by flow cytometry. Results We observed that the IL-15Cx modulates lung and systemic inflammation by increasing NK cells, CD8+ memory T cells and regulatory cells. However, IL-15Cx displays no effect on bronchial hyperreactivity, bronchial remodeling nor cellular bronchial infiltrate, but limits the secretion of bronchial mucus and modulates only inflammatory response in a HDM-allergic asthma murine model. Conclusions IL-15Cx has a limited effect on immune response in asthma and has no effect on lung function in mice. Thus, it limits its therapeutic potential but might suggest a combinatory potential with other therapeutics