Cannabinoid WIN55212‐2 impairs peanut‐allergic sensitization and promotes the generation of allergen‐specific regulatory T cells. Issue 4 (23rd January 2022) - Angelina, Alba
Abstract: 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, haematocrit, 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. Abstract : Peanut allergy represents the most common cause of food‐induced anaphylaxis. We show that the synthetic cannabinoid WIN55212‐2 reduces peanut‐induced human dendritic cell maturation and promotes the generation of regulatory T cells (Tregs), while reducing IL‐5‐producing T cells. In vivo, the administration of WIN55212‐2 during epicutaneous peanut sensitization in mice decreases the induction of peanut‐specific IgE and IgG1 antibodies in serum and promotes the generation of allergen‐specific FOXP3 + Tregs. Our data indicate that WIN55212‐2 interferes with peanut sensitization promoting tolerogenic responses.