Epicutaneous allergen immunotherapy induces a profound and selective modulation in skin dendritic-cell subsets.

Autor: Laoubi L; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France; DBV Technologies, Montrouge, France., Lacoffrette M; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France., Valsesia S; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France., Lenief V; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France., Guironnet-Paquet A; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France., Mosnier A; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France., Dubois G; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France., Cartier A; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France., Monti L; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France., Marvel J; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France., Espinosa E; Inserm, U1037, Centre de Recherche en Cancérologie de Toulouse (CRCT), Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France., Malissen B; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France., Henri S; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France., Mondoulet L; DBV Technologies, Montrouge, France., Sampson HA; DBV Technologies, Montrouge, France; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY., Nosbaum A; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France; Allergology and Clinical Immunology Department, Lyon Sud University Hospital, Pierre Bénite, France., Nicolas JF; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France; Allergology and Clinical Immunology Department, Lyon Sud University Hospital, Pierre Bénite, France., Dioszeghy V; DBV Technologies, Montrouge, France., Vocanson M; CIRI-Centre International de Recherche en Infectiologie, Lyon, France; INSERM, U1111, Lyon, France; University of Lyon, Lyon, France; Université de Lyon 1, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; CNRS, UMR 5308, Lyon, France. Electronic address: marc.vocanson@inserm.fr.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2022 Nov; Vol. 150 (5), pp. 1194-1208. Date of Electronic Publication: 2022 Jun 30.
DOI: 10.1016/j.jaci.2022.05.025
Abstrakt: Background: Epicutaneous immunotherapy (EPIT) protocols have recently been developed to restore tolerance in patients with food allergy. The mechanisms by which EPIT protocols promote desensitization rely on a profound immune deviation of pathogenic T- and B-cell responses.
Objective: To date, little is known about the contribution of skin dendritic cells (skDCs) to T-cell remodeling and EPIT efficacy.
Methods: We capitalized on a preclinical model of food allergy to ovalbumin (OVA) to characterize the phenotype and functions of OVA + skDCs throughout the course of EPIT.
Results: Our results showed that both Langerhans cells and dermal conventional cDC1 and cDC2 subsets retained their ability to capture OVA in the skin and to migrate toward the skin-draining lymph nodes during EPIT. However, their activation/maturation status was significantly impaired, as evidenced by the gradual and selective reduction of CD86, CD40, and OVA protein expression in respective subsets. Phenotypic changes during EPIT were also characterized by a progressive diversification of single-cell gene signatures within each DC subset. Interestingly, we observed that OVA + Langerhans cells progressively lost their capacity to prime CD4 + T EFF cells, but gained regulatory T-cell stimulatory properties. In contrast, cDC1 were inefficient in priming CD4 + T EFF cells or in reactivating T MEM cells in vitro, whereas cDC2 retained moderate stimulatory properties, and progressively biased type 2 immunity toward type 1 and type 17 responses.
Conclusions: Our results therefore emphasize that the acquisition of distinct phenotypic and functional specializations by skDCs during EPIT is at the cornerstone of the desensitization process.
(Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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