title: Oral macrophage-like cells play a key role in tolerance induction following sublingual immunotherapy of asthmatic mice.
abstract: 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.
authors.affiliation: Research and Development, Stallergènes SA, Antony, France.
authors.forename: L
authors.initials: L
authors.lastname: Mascarell
authors.forename: N
authors.initials: N
authors.lastname: Saint-Lu
authors.forename: H
authors.initials: H
authors.lastname: Moussu
authors.forename: A
authors.initials: A
authors.lastname: Zimmer
authors.forename: A
authors.initials: A
authors.lastname: Louise
authors.forename: Y
authors.initials: Y
authors.lastname: Lone
authors.forename: D
authors.initials: D
authors.lastname: Ladant
authors.forename: C
authors.initials: C
authors.lastname: Leclerc
authors.forename: S
authors.initials: S
authors.lastname: Tourdot
authors.forename: L
authors.initials: L
authors.lastname: Van Overtvelt
authors.forename: P
authors.initials: P
authors.lastname: Moingeon
mesh_terms: D000286:Administration, Sublingual; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D017951:Antigen Presentation; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009061:Mouth Mucosa / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000485:Allergens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D010047:Ovalbumin