4.4 Article

Sublingual administration of liposomes enclosing alpha-galactosylceramide as an effective adjuvant of allergen immunotherapy in a murine model of allergic rhinitis

Journal

ALLERGOLOGY INTERNATIONAL
Volume 68, Issue 3, Pages 352-362

Publisher

JAPANESE SOCIETY ALLERGOLOGY
DOI: 10.1016/j.alit.2019.02.003

Keywords

Allergic; Liposome; Mice; Natural killer T-Cells; Rhinitis

Funding

  1. Japan Agency for Medical Research and Development (AMED)
  2. Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan

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Background: Sublingual immunotherapy (SLIT) is an established efficacious approach for the treatment of allergic rhinitis (AR). However, SLIT requires a long administration period to establish stable and adequate responses. This study investigated the efficacy of the sublingual administration of an allergen with liposomes enclosing alpha-GalCer (alpha-GC-liposome) as a potential adjuvant in mice with AR. Methods: Mice with AR induced by OVA received the sublingual administration of OVA, alpha-GC-liposomes, or OVA plus alpha-GC-liposomes for 7 days. After nasal re-challenge with OVA, nasal symptoms were evaluated. The serum levels of OVA-specific Ig, the cytokine production of CD4+ T cells in the cultures of cervical lymph node (CLN) cells, and the gene expression of CLNs were analyzed. Results: Although IL-4, IL-5 and IL-13 production from CD4+ T cells in CLN cells was significantly inhibited by the sublingual administration of OVA alone in mice with AR induced by OVA, their nasal symptoms were not significantly diminished. However, the combined sublingual administration of alpha-GC-liposomes and OVA completely suppressed nasal symptoms, downregulated Th2 and Th17 type cytokine production in CD4+ T cells as well as Th2 and Th17 gene expressions, and upregulated Th1 type cytokine production as well as Th1 gene expressions in CLN cells. Additionally, the serum levels of specific IgG2a were promoted, and specific IgE and IgG1 were inhibited. Conclusions: Our findings suggest that the sublingual administration of an allergen with alpha-GC-liposomes as an adjuvant might increase the therapeutic efficacy and effectiveness of this treatment method. Copyright (C) 2019, Japanese Society of Allergology. Production and hosting by Elsevier B.V.

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