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



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Angelina Querencias, Alba and Jiménez Saiz, Rodrigo and Pérez Diego, Mario and Maldonado, Ángel and Rückert, Beate and Akdis, Mübeccel and Martín Fontecha, María del Mar and Akdis, Cezmi A. and Palomares, Oscar (2022) Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells. Clinical and Experimental Allergy . 10 p.. ISSN 0954-7894 (In Press)

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Background: Cannabinoids are lipid-derived mediators with anti-inflammatory prop-erties in different diseases. WIN55212-2, a non-selective synthetic cannabinoid, re-duces immediate anaphylactic reactions in a mouse model of peanut allergy, but its capacity to prevent peanut-allergic sensitization and the underlying mechanisms re-mains 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 epicuta-neously 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 quanti-fied. 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 sensi-tization and promotes tolerogenic responses, which might well pave the way for the development of novel prophylactic and therapeutic strategies for peanut allergy.

Item Type:Article
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CRUE-CSIC (Acuerdos Transformativos 2022)

Uncontrolled Keywords:cannabinoids, dendritic cells, peanut allergy, regulatory T cells
Subjects:Sciences > Chemistry > Chemistry, Organic
Medical sciences > Medicine > Allergy
Medical sciences > Medicine > Immunology
ID Code:70265
Deposited On:24 Feb 2022 13:51
Last Modified:15 Jun 2022 07:56

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