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 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 an...

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Autores: Angelina Querencias, Alba, Jiménez Saiz, Rodrigo, Pérez Diego, Mario, Maldonado, Ángel, Rückert, Beate, Akdis, Mübeccel, Martín-Fontecha Corrales, María Del Mar, Akdis, Cezmi A., Palomares Gracia, Óscar
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/71298
Acceso en línea:https://hdl.handle.net/20.500.14352/71298
Access Level:acceso abierto
Palabra clave:633.888:616-056.3
577.27
634.58
612.112
cannabinoids
dendritic cells
peanut allergy
regulatory T cells
Química orgánica (Química)
Alergología
Inmunología
2306 Química Orgánica
3207.01 Alergias
2412 Inmunología
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oai_identifier_str oai:docta.ucm.es:20.500.14352/71298
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network_name_str España
repository_id_str
spelling Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cellsAngelina Querencias, AlbaJiménez Saiz, RodrigoPérez Diego, MarioMaldonado, ÁngelRückert, BeateAkdis, MübeccelMartín-Fontecha Corrales, María Del MarAkdis, Cezmi A.Palomares Gracia, Óscar633.888:616-056.3577.27634.58612.112cannabinoidsdendritic cellspeanut allergyregulatory T cellsQuímica orgánica (Química)AlergologíaInmunología2306 Química Orgánica3207.01 Alergias2412 InmunologíaBackground: 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.WileyUniversidad Complutense de Madrid20222022-01-0720222022-01-07journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/71298reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial 3.0 Españahttps://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/712982026-06-02T12:44:21Z
dc.title.none.fl_str_mv Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells
title Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells
spellingShingle Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells
Angelina Querencias, Alba
633.888:616-056.3
577.27
634.58
612.112
cannabinoids
dendritic cells
peanut allergy
regulatory T cells
Química orgánica (Química)
Alergología
Inmunología
2306 Química Orgánica
3207.01 Alergias
2412 Inmunología
title_short Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells
title_full Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells
title_fullStr Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells
title_full_unstemmed Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells
title_sort Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells
dc.creator.none.fl_str_mv Angelina Querencias, Alba
Jiménez Saiz, Rodrigo
Pérez Diego, Mario
Maldonado, Ángel
Rückert, Beate
Akdis, Mübeccel
Martín-Fontecha Corrales, María Del Mar
Akdis, Cezmi A.
Palomares Gracia, Óscar
author Angelina Querencias, Alba
author_facet Angelina Querencias, Alba
Jiménez Saiz, Rodrigo
Pérez Diego, Mario
Maldonado, Ángel
Rückert, Beate
Akdis, Mübeccel
Martín-Fontecha Corrales, María Del Mar
Akdis, Cezmi A.
Palomares Gracia, Óscar
author_role author
author2 Jiménez Saiz, Rodrigo
Pérez Diego, Mario
Maldonado, Ángel
Rückert, Beate
Akdis, Mübeccel
Martín-Fontecha Corrales, María Del Mar
Akdis, Cezmi A.
Palomares Gracia, Óscar
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 633.888:616-056.3
577.27
634.58
612.112
cannabinoids
dendritic cells
peanut allergy
regulatory T cells
Química orgánica (Química)
Alergología
Inmunología
2306 Química Orgánica
3207.01 Alergias
2412 Inmunología
topic 633.888:616-056.3
577.27
634.58
612.112
cannabinoids
dendritic cells
peanut allergy
regulatory T cells
Química orgánica (Química)
Alergología
Inmunología
2306 Química Orgánica
3207.01 Alergias
2412 Inmunología
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-01-07
2022
2022-01-07
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/71298
url https://hdl.handle.net/20.500.14352/71298
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial 3.0 España
https://creativecommons.org/licenses/by-nc/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial 3.0 España
https://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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