Mechanism differences in the start time of sublingual immunotherapy in a mouse allergic airway inflammation model

Autor: Akira Saito, Toshiyuki Koya, Ami Aoki, Shun Naramoto, Hiroshi Ueno, Yuki Nishiyama, Kenjiro Shima, Yosuke Kimura, Takashi Hasegawa, Satoshi Watanabe, Yasuyoshi Ohshima, Keisuke Suzuki, Katsuyo Ohashi-Doi, Toshiaki Kikuchi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-78062-6
Popis: Abstract Sublingual immunotherapy (SLIT) has received considerable attention as a method for allergen immunotherapy (AIT). However, the mechanism of SLIT, especially its timing, has not been thoroughly investigated. We evaluated therapeutic and prophylactic SLIT in an allergic airway inflammation model and evaluated their efficacies. Mice were intranasally exposed to Dermatophagoides farinae (Der f) extract and received SLIT before (prophylactic model) and after (therapeutic model) intranasal exposure of Der f. We investigated airway responsiveness, airway inflammation, allergen-specific antibodies, lung histology and single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing were also investigated. SLIT in the therapeutic model was effective; however, the effects of SLIT in the prophylactic model were stronger and immune tolerance was maintained for three months. ScRNA-seq of lung CD4+CD25+ T cells revealed that the expansion of induced T regulatory (iTreg) cells was greater in the prophylactic model than that in the therapeutic model. Additionally, the TCR repertoire of iTregs from the prophylactic model was abundant, sharing many clones with the TCR repertoire of effector T cells. These data suggest that the prophylactic model of AIT is extremely effective and persistent, and may respond to allergen diversity, and provide evidence for the clinical recommendation of preventive AIT.
Databáze: Directory of Open Access Journals
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