A۲ adenosine receptor contributes to the development of cow’s milk protein allergy via regulating regulatory T cells

Objective(s): A۲ adenosine receptor (A۲AR) is a novel promising target for the treatment of inflammatory and allergic diseases. However, its role in the development of cow’s milk protein allergy (CMPA) has not been elucidated. The present study was designed to investigate the function of A۲AR in CMPA development.Materials and Methods: BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic responses. The model was assessed by detecting allergic responses and plasma-specific IgE levels. The levels of A۲AR were measured by PCR and flow cytometry. The subpopulation of Treg cells was analysed.Results: The mice sensitized and challenged with OVA showed classic allergic symptoms, such as acute allergic skin responses, increased anaphylactic shock symptom scores, and higher levels of total IgE, OVA-specific IgE, IgG۱ and IgG۲a. OVA-sensitized mice and CMPA patients showed decreased levels of A۲AR and Treg cells. Interestingly, we observed a positive correlation between A۲AR expression and Treg levels in CMPA patients. Further study showed that the A۲AR agonist CGS۲۱۶۸۰ blocked OVA-induced allergic reactions, and the A۲AR antagonist KW-۶۰۰۲ amplified allergic responses. Interestingly, CGS۲۱۶۸۰ not only activated the A۲AR-mediated signalling pathway but also caused an increase in the population of Treg cells. In contrast, KW-۶۰۰۲ therapy decreased the levels of Tregs in allergic mice.Conclusion: A۲AR expression is downregulated in CMPA. The A۲AR-mediated pathway negatively regulates the development of CMPA, at least in part, by amplifying the differentiation of Tregs.

Keywords:

Adenosine receptor , Allergic response , Cow’s milk protein allergy , FOXP۳ , Regulatory T cells