Oral macrophage-like cells play a key role in tolerance induction following sublingual immunotherapy of asthmatic mice

• Published in: Mucosal immunology Vol. 4; no. 6; pp. 638 - 647
• Main Authors: Mascarell, L, Saint-Lu, N, Moussu, H, Zimmer, A, Louise, A, Lone, Y, Ladant, D, Leclerc, C, Tourdot, S, Van Overtvelt, L, Moingeon, P
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2011; Elsevier Limited
• Subjects: 631/250/2152/569; 631/250/251; 692/698/690/292; 692/699/249/2510/31; Administration, Sublingual; Allergens - administration & dosage; Allergology; Animals; Antibodies; Antigen Presentation; Asthma - chemically induced; Asthma - drug therapy; Asthma - immunology; Asthma - physiopathology; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Cytokines - metabolism; Desensitization, Immunologic; Disease Models, Animal; Forkhead Transcription Factors - metabolism; Gastroenterology; Humans; Immune Tolerance; Immunology; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Mouth Mucosa - pathology; Ovalbumin - administration & dosage; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2011.28

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.