부산대학교 도서관

Sublingual allergen-specific immunotherapy (SLIT) is a safe and efficacious treatment for type 1 respiratory allergies. Herein, we investigated the key subset(s) of antigen-presenting cells (APCs) involved in antigen/allergen capture and tolerance induction during SLIT. Following sublingual administration, fluorochrome-labeled ovalbumin (OVA) is predominantly captured by oral CD11b+CD11c− cells that migrate to cervical lymph nodes (CLNs) and present the antigen to naive CD4+ T cells. Conditional depletion with diphtheria toxin of CD11b+, but not CD11c+ cells, in oral tissues impairs CD4+ T-cell priming in CLNs. In mice with established asthma to OVA, specific targeting of the antigen to oral CD11b+ cells using the adenylate cyclase vector system reduces airway hyperresponsiveness (AHR), eosinophil recruitment in bronchoalveolar lavages (BALs), and specific Th2 responses in CLNs and lungs. Oral CD11b+CD11c− cells resemble tolerogenic macrophages found in the lamina propria (LP) of the small intestine in that they express the mannose receptor CD206, as well as class-2 retinaldehyde dehydrogenase (RALDH2), and they support the differentiation of interferon-γ/interleukin-10 (IFNγ/IL-10)-producing Foxp3+ CD4+ regulatory T cells. Thus, among the various APC subsets present in oral tissues of mice, macrophage-like cells play a key role in tolerance induction following SLIT. [ABSTRACT FROM AUTHOR]