Person: Pérez Diego, Mario
Universidad Complutense de Madrid
Faculty / Institute
Bioquímica y Biología Molecular
Now showing 1 - 5 of 5
- PublicationCannabinoids induce functional Tregs by promoting tolerogenic DCs via autophagy and metabolic reprograming(Springer Nature, 2021-09-21) Angelina Querencias, Alba; Pérez Diego, Mario; López Abente, Jacobo; Rückert, Beate; Nombela, Iván; Akdis, Mübeccel; Martín Fontecha, María del Mar; Akdis, Cezmi A.; Palomares, OscarThe generation of functional regulatory T cells (Tregs) is essential to keep tissue homeostasis and restore healthy immune responses in many biological and inflammatory contexts. Cannabinoids have been pointed out as potential therapeutic tools for several diseases. Dendritic cells (DCs) express the endocannabinoid system, including the cannabinoid receptors CB1 and CB2. However, how cannabinoids might regulate functional properties of DCs is not completely understood. We uncover that the triggering of cannabinoid receptors promote human tolerogenic DCs that are able to prime functional FOXP3+ Tregs in the context of different inflammatory diseases. Mechanistically, cannabinoids imprint tolerogenicity in human DCs by inhibiting NF-κB, MAPK and mTOR signalling pathways while inducing AMPK and functional autophagy flux via CB1- and PPARα-mediated activation, which drives metabolic rewiring towards increased mitochondrial activity and oxidative phosphorylation. Cannabinoids exhibit in vivo protective and anti-inflammatory effects in LPS-induced sepsis and also promote the generation of FOXP3+ Tregs. In addition, immediate anaphylactic reactions are decreased in peanut allergic mice and the generation of allergen-specific FOXP3+ Tregs are promoted, demonstrating that these immunomodulatory effects take place in both type 1- and type 2-mediated inflammatory diseases. Our findings might open new avenues for novel cannabinoid-based interventions in different inflammatory and immune-mediated diseases.
- PublicationCannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells(Wiley, 2022-01-07) Angelina Querencias, Alba; Jiménez Saiz, Rodrigo; Pérez Diego, Mario; Maldonado, Ángel; Rückert, Beate; Akdis, Mübeccel; Martín Fontecha, María del Mar; Akdis, Cezmi A.; Palomares, OscarBackground: 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.
- PublicationThe cannabinoid WIN55212-2 suppresses effector T-cell responses and promotes regulatory T cells in human tonsils(John Wiley & Sons, 2021-10-28) Angelina Querencias, Alba; Pérez Diego, Mario; Maldonado, Ángel; Rückert, Beate; Akdis, Mübeccel; Martín Fontecha, María del Mar; Akdis, Cezmi A.; Palomares, Oscar
- PublicationAllergoid–mannan conjugates reprogram monocytes into tolerogenic dendritic cells via epigenetic and metabolic rewiring(Elsevier, 2022-06-18) Benito Villalvilla, Cristina; Pérez Diego, Mario; Angelina Querencias, Alba; Kisand, Kai; Rebane, Ana; Subiza, José Luis; Palomares Gracia, OscarAllergoid–mannan conjugates are novel vaccines for allergen-specific immunotherapy being currently assayed in phase 2 clinical trials. Allergoid–mannan conjugates target dendritic cells (DCs) and generate functional forkhead box P3 (FOXP3)-positive Treg cells, but their capacity to reprogram monocyte differentiation remains unknown.
- PublicationThe cannabinoid WIN55212-2 restores rhinovirus-induced epithelial barrier disruption(John Wiley & Sons, 2020-12-15) Angelina Querencias, Alba; Martín Fontecha, María del Mar; Rückert, Beate; Wawrzyniak, Paulina; Pérez Diego, Mario; López Abente, Jacobo; Akdis, Mübeccel; Akdis, Cezmi A.; Palomares, Oscar