Artikel ; Online: Comprehensive mapping of immune tolerance yields a regulatory TNF receptor 2 signature in a murine model of successful Fel d 1-specific immunotherapy using high-dose CpG adjuvant.
2021 Band 76, Heft 7, Seite(n) 2153–2165
Abstract: Background: The prevalence of allergy to cat is expanding worldwide. Allergen-specific immunotherapy (AIT) has advantages over symptomatic pharmacotherapy and promises long-lasting disease control in allergic patients. However, there is still a need to ... ...
| Abstract | Background: The prevalence of allergy to cat is expanding worldwide. Allergen-specific immunotherapy (AIT) has advantages over symptomatic pharmacotherapy and promises long-lasting disease control in allergic patients. However, there is still a need to improve cat AIT regarding efficacy, safety, and adherence to the treatment. Here, we aim to boost immune tolerance to the major cat allergen Fel d 1 by increasing the anti-inflammatory activity of AIT with the established immunomodulatory adjuvant CpG, but at a higher dose than previously used in AIT. Methods: Together with CpG, we used endotoxin-free Fel d 1 as therapeutic allergen throughout the study in a BALB/c model of allergy to Fel d 1, thus mimicking the conditions of human AIT trials. Multidimensional immune phenotyping including mass cytometry (CyTOF) was applied to analyze AIT-specific immune signatures. Results: We show that AIT with high-dose CpG in combination with endotoxin-free Fel d 1 reverts all major hallmarks of allergy. High-dimensional CyTOF analysis of the immune cell signatures initiating and sustaining the AIT effect indicates the simultaneous engagement of both, the pDC-Treg and B-cell axis, with the emergence of a systemic GATA3 Conclusion: Our results highlight the potential of CpG adjuvant in a novel formulation to be further exploited for inducing allergen-specific tolerance in patients with cat allergy or other allergic diseases. |
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| Mesh-Begriff(e) | Allergens ; Animals ; Cats ; Desensitization, Immunologic ; Disease Models, Animal ; Glycoproteins/immunology ; Humans ; Hypersensitivity/therapy ; Immune Tolerance ; Mice ; Receptors, Tumor Necrosis Factor, Type II | ||||||||||
| Chemische Substanzen | Allergens ; Glycoproteins ; Receptors, Tumor Necrosis Factor, Type II ; Fel d 1 protein, Felis domesticus (G408EE88II) | ||||||||||
| Sprache | Englisch | ||||||||||
| Erscheinungsdatum | 2021-01-05 | ||||||||||
| Erscheinungsland | Denmark | ||||||||||
| Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 391933-x | ||||||||||
| ISSN | 1398-9995 ; 0105-4538 | ||||||||||
| ISSN (online) | 1398-9995 | ||||||||||
| ISSN | 0105-4538 | ||||||||||
| DOI | 10.1111/all.14716 | ||||||||||
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| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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