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

Alba Angelina; Rodrigo Jiménez‐Saiz; Mario Pérez‐DiegoAngel MaldonadoBeate RückertMübeccel AkdisMar Martín‐FontechaCezmi A. AkdisOscar Palomares

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

机译：Cannabinoid WIN55212‐2 impairs peanut‐allergic sensitization and promotes the generation of allergen‐specific regulatory T cells

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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.

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《Clinical and experimental allergy》 |2022年第4期|540-549|共10页
作者
Alba Angelina; Rodrigo Jiménez‐Saiz; Mario Pérez‐DiegoAngel MaldonadoBeate RückertMübeccel AkdisMar Martín‐FontechaCezmi A. AkdisOscar Palomares;
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作者单位

Department of Biochemistry and Molecular Biology,Complutense University of Madrid;

Swiss Institute of Allergy and Asthma Research (SIAF),University of Zürich;

Department of Organic Chemistry,Complutense University of Madrid;

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正文语种英语
中图分类医学免疫学;
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cannabinoids; dendritic cells; peanut allergy; regulatory T cells;

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

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