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

IL-15 / sIL-15Rα 复合物调节小鼠免疫力,但不影响哮喘特征

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作者:Antoine Moui, Martin Klein, Dorian Hassoun, Eléonore Dijoux, Marie-Aude Cheminant, Antoine Magnan, Grégory Bouchaud

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

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.

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.

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