Cannabinoid WIN55212‐2 impairs peanut‐allergic sensitization and promotes the generation of allergen‐specific regulatory T cells Academic Article uri icon

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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.

authors

  • Jimenez Saiz, Rodrigo
  • Angelina, Alba
  • Jiménez‐Saiz, Rodrigo
  • Pérez‐Diego, Mario
  • Maldonado, Angel
  • Rückert, Beate
  • Akdis, Mübeccel
  • Martín‐Fontecha, Mar
  • Akdis, Cezmi A
  • Palomares, Oscar

publication date

  • April 2022