Abstract
Programmed cell death ligand 1(PDL-1) is known for its inhibitory effect on the cellular immune response. Even though it is expressed on the surface of mast cells, its role in allergic diseases is unknown. We analyzed the effects of PD-L1 blockade in a murine model of active cutaneous anaphylaxis (ACA). C57BL/6 mice were sensitized and challenged with ovalbumin (OVA). Blood samples were collected to measure specific immunoglobulins. The mice were divided into six groups that underwent the active cutaneous anaphylaxis procedure. Group 1 (negative control) received 50 μl of phosphate-buffered saline (PBS) subcutaneously, and the other five groups were sensitized with 50 μg of OVA subcutaneously. Group 2 was the positive control, and the others received the anti-PD-L1 antibody or its isotype during sensitization (groups 3 and 4) or during the challenge (groups 5 and 6). All animals that underwent ACA on the ears with OVA and PBS were sacrificed, and the reaction was evaluated by extravasation of Evans blue (measured by spectrophotometry) and histological analysis of the collected fragments. Anti-PD-L1 blockade during the sensitization phase led to a reduction in specific IgE and IgG1 levels, allergic reaction intensity at the ACA site, and mast cell degranulation in the tissue. There was no significant biological effect of anti-PD-L1 administration on the challenge phase. PD-L1 blockade during allergen sensitization inhibited the synthesis of specific IgE and IgG1 and decreased mast cell activation in this murine model of anaphylaxis.
Highlights
Anaphylaxis is an immediate systemic hypersensitivity reaction induced by mast cell and basophil degranulation and is a medical emergency that can lead to death [1, 2]
Specific immunoglobulin E (IgE) levels from anti-programmed cell death ligand 1 (PD-L1) group increased in D27, reaching higher levels than the negative control group, they were lower than the positive control and anti-PD-L1 isotype groups (Figure 3)
Our study suggests that PD-L1 plays a crucial role in the activation of the Th2 immune response profile
Summary
Anaphylaxis is an immediate systemic hypersensitivity reaction induced by mast cell and basophil degranulation and is a medical emergency that can lead to death [1, 2]. Studies have shown a growing incidence and mortality of anaphylactic reactions, especially those induced by drugs and food [2]. Animal models are essential to better understand the pathophysiological mechanisms involved in diseases and to evaluate the safety and efficacy of new therapies before starting clinical trials in humans. Anaphylaxis has been reproduced and analyzed in murine models thanks to the practicality of rearing, breeding, maintaining, and handling these animals and their availability, including knockout and transgenic models [3]. Several animal models have been developed to study the mechanisms involved in allergic inflammation, including models of respiratory and food allergies and systemic and local anaphylaxis [3,4,5,6,7,8]. Cutaneous anaphylaxis induced in animal models can be divided into active and passive anaphylaxis. In the active cutaneous anaphylaxis (ACA) model, mice are sensitized by receiving fractionated doses of the allergen, whereas in the passive cutaneous anaphylaxis (PCA) model, the animals are passively sensitized by receiving serum from other mice that were previously actively sensitized [9]
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