TY - JOUR
T1 - Epicutaneous allergen immunotherapy induces a profound and selective modulation in skin dendritic-cell subsets
AU - Laoubi, Léo
AU - Lacoffrette, Morgane
AU - Valsesia, Séverine
AU - Lenief, Vanina
AU - Guironnet-Paquet, Aurélie
AU - Mosnier, Amandine
AU - Dubois, Gwendoline
AU - Cartier, Anna
AU - Monti, Laurine
AU - Marvel, Jacqueline
AU - Espinosa, Eric
AU - Malissen, Bernard
AU - Henri, Sandrine
AU - Mondoulet, Lucie
AU - Sampson, Hugh A.
AU - Nosbaum, Audrey
AU - Nicolas, Jean François
AU - Dioszeghy, Vincent
AU - Vocanson, Marc
N1 - Publisher Copyright:
© 2022 American Academy of Allergy, Asthma & Immunology
PY - 2022/11
Y1 - 2022/11
N2 - 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+ TEFF cells, but gained regulatory T-cell stimulatory properties. In contrast, cDC1 were inefficient in priming CD4+ TEFF cells or in reactivating TMEM 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.
AB - 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+ TEFF cells, but gained regulatory T-cell stimulatory properties. In contrast, cDC1 were inefficient in priming CD4+ TEFF cells or in reactivating TMEM 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.
KW - Food allergy
KW - T-cell responses
KW - allergen immunotherapy
KW - desensitization
KW - epicutaneous immunotherapy
KW - skin dendritic cells
UR - http://www.scopus.com/inward/record.url?scp=85140449549&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2022.05.025
DO - 10.1016/j.jaci.2022.05.025
M3 - Article
C2 - 35779666
AN - SCOPUS:85140449549
SN - 0091-6749
VL - 150
SP - 1194
EP - 1208
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -