The cannabinoid WIN55212-2 impairs peanut allergic sensitization and promotes the generation of allergen-specific regulatory T cells

Background: Cannabinoids are lipid-derived mediators with anti-inflammatory properties in different diseases. WIN55212-2, a non-selective synthetic cannabinoid, reduces immediate anaphylactic reactions in a mouse model of peanut allergy, but its capacity to prevent peanut allergic sensitization and the underlying mechanisms remains largely unknown.

Objective: To investigate the capacity of WIN55212-2 to immunomodulate peanut-stimulated human dendritic cells (DCs) and peanut allergic sensitization in mice.

Methods: Surface markers and cytokines were quantified by flow cytometry, ELISA and qPCR in human monocyte-derived DCs (hmoDCs) and T cell cocultures after stimulation with peanut alone or in the presence of WIN55212-2. Mice were epicutaneously sensitized with peanut alone or peanut/WIN55212-2. After peanut challenge, drop in body temperature, hematocrit, clinical symptoms, peanut-specific antibodies in serum and FOXP3⁺ regulatory (Treg) cells in spleen and lymph nodes were quantified. Splenocytes were stimulated in vitro with peanut to analyse allergen-specific T cell responses.

Results: WIN55212-2 reduced peanut-induced hmoDC activation and promoted the generation of CD4⁺ CD127^– CD25⁺ FOXP3⁺ Treg cells, while reducing the induction of IL-5-producing T cells. In vivo, WIN55212-2 impaired the peanut-induced migration of DCs to lymph nodes and their maturation. WIN55212-2 significantly reduced the induction of peanut-specific IgE and IgG₁ antibodies in serum during epicutaneous peanut sensitization, reduced the clinical symptoms score upon peanut challenge and promoted the generation of allergen-specific FOXP3⁺ Treg cells.

Conclusions: The synthetic cannabinoid WIN55212-2 interferes with peanut sensitization and promotes tolerogenic responses, which might well pave the way for the development of novel prophylactic and therapeutic strategies for peanut allergy.