IL-2-Agonist-Induced IFN-γ Exacerbates Systemic Anaphylaxis in Food Allergen-Sensitized Mice

Abstract

Food allergies are common, costly and potentially life-threatening disorders. They are driven by Th2, but inhibited by Th1 reactions. There is also evidence indicating that IL-2 agonist treatment inhibits allergic sensitization through expansion of regulatory T cells. Here, we tested the impact of an IL-2 agonist in a novel model for food allergy to hen´s egg in mice sensitized without artificial adjuvants. Prophylactic IL-2 agonist treatment expanded Treg populations and inhibited allergen-specific sensitization. However, IL-2 agonist treatment of already sensitized mice increased mast cell responses and allergic anaphylaxis upon allergen re-challenge. These effects depended on allergen-specific IgE and were mediated through IFN-γ, as shown by IgE transfer and blockade of IFN-γ with monoclonal antibodies. These results suggest that although shifting the allergic reaction toward a Treg/Th1 response inhibits allergic sensitization, the prototypic Th1 cytokine IFN-γ promotes mast cell activation and allergen-induced anaphylaxis in individuals that are already IgE-sensitized. Hence, while a Th1 response can prevent the development of food allergy, IFN-γ has the ability to exacerbate already established food allergy.

Clinical efficacy of thymosin alpha 1 combined with multi-modality chemotherapy and its effects on immune function of patients with pulmonary tuberculosis complicated with diabetes

“…IL-2 and IFN-γ support Th1 cell proliferation and antagonize the effects of IL-4 and TNF-α. 25 All this conforms with the findings of this study: the Tα1 group had lower sputum supernatant levels of IL-4 and TNF-α but higher sputum supernatant levels of IL-2 and IFN-γ compared with the control group. Previous studies have also shown that Tα1 can reduce liver inflammation and reduce hepatocyte apoptosis by down-regulating TNF-α and up-regulating IL-10.…”

Single-dose AAV vector gene immunotherapy to treat food allergy

“…In the control group we observed an elevation in both IFNγ and IL-10, which is typically associated with the suppression of Th2 responses. Here we hypothesize that IFNγ may be acting as an enhancer of mast cell degranulation 56 and IL-10 may be proinflammatory under certain conditions, as it was shown to play a critical role in the development of Th2 responses in an allergic dermatitis mouse model. 57 …”

“…In the control group we observed an elevation in both IFNg and IL-10, which is typically associated with the suppression of Th2 re-sponses. Here we hypothesize that IFNg may be acting as an enhancer of mast cell degranulation 56 and IL-10 may be proinflammatory under certain conditions, as it was shown to play a critical role in the development of Th2 responses in an allergic dermatitis mouse model. 57 Immune tolerance in the context of hepatic AAV gene delivery is predicated on a number of variables including, but not limited to, the AAV capsid, promoter, and transgene product expression levels.…”

COVID-19-associated opportunistic infections: a snapshot on the current reports

“…Hyperinflammation and cytokine storm syndrome (CSS) are among the major causes of acute respiratory distress syndrome (ARDS), multiorgan failure, and death due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [ 13 – 15 ]. An unexpected increase in the circulating levels of proinflammatory cytokines, especially interleukin-1 (IL-1), IL-6, gamma interferon (IFN γ ) and tumor necrosis factor- α (TNF- α ), leads to hyperinflammation and the CSS [ 16 ]. When CSS occurs, different immune cells ( e.g., neutrophils, macrophages, and T cells) infiltrate into the site of infection, and consequently, a cascade of damage of the vascular barrier, diffuse alveolar damage and lung injury, multiorgan failure, and ultimately death occurs [ 17 ].…”

“…When CSS occurs, different immune cells ( e.g., neutrophils, macrophages, and T cells) infiltrate into the site of infection, and consequently, a cascade of damage of the vascular barrier, diffuse alveolar damage and lung injury, multiorgan failure, and ultimately death occurs [ 17 ]. ARDS is one of the major consequences of CSS that directly link to severe sequel and mortality in acute COVID-19 patients [ 13 , 16 ]. Therefore, therapeutic strategies to mitigate the risk of CSS and ARDS are essential.…”