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

Abstract

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.

Current Strategies to Modulate Regulatory T Cell Activity in Allergic Inflammation

“…In both models, the suppressive function of Treg could further be enhanced by the CD4-binding HIV-1 surface protein gp120, preventing GvHD or allergic airway inflammation, respectively (79,80). Recently, it has been reported that low-dose IL-2 or a combination of IL-2/anti-IL-2 restored Treg numbers and function in respiratory and food allergies, thereby improving allergic markers and symptoms (81)(82)(83). Manipulation of the intestinal microbiota associated with induction or expansion of Treg cells as shown in numerous animal models of allergy and asthma may also offer novel strategies for immunomodulation of food allergies.…”

The T-Cell Growth Factor Interleukin-2, Which Is Occasionally Targeted by Autoantibodies, Qualifies as Drug for the Treatment of Allergy, Autoimmunity, and Cancer: Collegium Internationale Allergologicum (CIA) Update 2024

“…1 ). In preclinical models, IL-2C-expanded Tregs not only protected from experimental autoimmune encephalitis and prolonged survival of allogeneic islet grafts [ 45 ] but also ameliorated allergen-induced airway hyperreactivity in prophylactic and therapeutic settings, where they reduced allergen-specific IgE serum levels [ 46 , 47 ] and expanded Treg during sublingual immunotherapy [ 48 ] and food allergy, respectively [ 49 ]. Moreover, it was shown that IL-2C-expanded Treg cells could be recalled upon allergen challenge, which was associated with suppression of lung-specific Th2 responses long after initial treatment [ 50 ].…”

The role of hypoxia in the pathophysiology of chronic rhinosinusitis

“…Treg cells are a subtype of T cells that maintain immune function and regulate immune adaptation. [177][178][179][180] The expression of Treg cells is closely related to the pathological state of the respiratory tract, and its functional impairment can potentially lead to autoimmune diseases. The increase of HIF-1α and HIF-2α in hypoxic conditions can inhibit the differentiation of Treg cells.…”