Engineering a safe monoclonal anti-human IL-2 that is effective in a murine model of food allergy and asthma

Background Regulatory T cells (Tregs) are known to protect against allergies. Moreover, the decrease in the frequency and efficiency of Tregs amplifies allergic symptoms. Aim This study investigated whether expanding Tregs in vivo with an IL-2/IL-2 antibody complex could be safe, well tolerated and efficient in a therapeutic setting in allergies. Methods We produced an anti-IL-2 antibody (1C6) and demonstrated that when it is complexed to human IL-2, it increases IL-2 efficiency to induce Tregs in vivo without any detectable side effects. Furthermore, the IL-2/1C6 complex induces an increase in Helios expression by Tregs, suggesting that it not only elevated Treg numbers but also boosted their functions. Using mouse models of house-dust-mite-induced airway inflammation and wheat-gliadin-induced food allergies, we investigated the therapeutic potential of the IL-2/1C6 complex in allergies. Results IL-2/1C6 treatment significantly reduced allergic symptoms, specific IgE production, the adaptive immune response and tissue damage. Interestingly, IL-2/1C6 treatment modulated innate lymphoid cells by increasing ILC2s in asthma and decreasing ILC3s in food allergies. Conclusion In conclusion,complexed IL-2/anti-IL-2 may restore Treg numbers and function in respiratory and food allergies, thereby improving allergic markers and symptoms. Our IL-2/anti-IL-2 complex offers new hope for reestablishing immune tolerance in patients with allergies.

Automated summary

The study investigated the therapeutic potential of expanding Tregs with an IL-2/IL-2 antibody complex in allergies. Results showed that the complex treatment significantly reduced allergic symptoms, specific IgE production, and tissue damage while modulating innate lymphoid cells. The IL-2/anti-IL-2 complex offers new hope for reestablishing immune tolerance in patients with allergies.