Regulatory dendritic cells protect against allergic airway inflammation in a murine asthmatic model

• Published in: Journal of allergy and clinical immunology Vol. 121; no. 1; pp. 95 - 104.e7
• Main Authors: Fujita, Shigeharu, MD, Yamashita, Naomi, MD, PhD, Ishii, Yasuyuki, PhD, Sato, Yumiko, Sato, Kaori, Eizumi, Kawori, Fukaya, Tomohiro, BVSc, Nozawa, Risa, Takamoto, Yukiko, Yamashita, Naohide, MD, PhD, Taniguchi, Masaru, MD, PhD, Sato, Katsuaki, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 2008; Elsevier; Elsevier Limited
• Subjects: Adoptive Transfer; airway hyperreactivity; Allergy and Immunology; Animals; Asthma - immunology; Biological and medical sciences; Bone marrow; Bronchial Hyperreactivity - immunology; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - transplantation; Disease Models, Animal; Experiments; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hypersensitivity - immunology; IgE; Immune system; Immunopathology; Inflammation - immunology; Lymphocytes; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T H2 cells; T regulatory cells; T-Lymphocytes, Regulatory; tolerance; Japan; airway hyperreactivity; IgE; DNP-OVA; Immature dendritic cell; Regulatory dendritic cell; Naturally occurring CD4 +CD25 +Foxp3 +T regulatory; T H2 cells; nTreg; Antigen-presenting cell; T regulatory; ICOS; WT; tolerance; maDC; Dendritic cell; Dendritic cells; BALF; Treg; Inducible costimulator; T FH; iDC; Mature dendritic cell; DCreg; T follicular helper; 2,4-Dinitrophenol–conjugated ovalbumin; Wild-type; APC; T regulatory cells; Bronchoalveolar lavage fluid; DC; Allergy; Animal model; Hyperreactivity; Treg cell; Helper cell; Respiratory system; Respiratory tract; TH2 cells; Immunology; Antigen presenting cell; Bronchus disease; Th2 lymphocyte; Obstructive pulmonary disease; Protection; Regulatory cell; Lung disease; Immunopathology; Respiratory disease; Rodentia; Tolerance; Inflammation; Asthma; Vertebrata; Mammalia; Mouse
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.08.038

Background Dendritic cells (DCs) are crucial for the induction of immunity and tolerance. Despite an improved understanding of the DC-mediated control of TH 1-biased immunity, little is known about how DCs regulate TH 2-mediated immunity. Objective The effects of immunostimulatory mature DCs (maDCs) and regulatory DCs (DCregs) on TH 2-driven allergic immunity involving IgE production were examined. Methods A murine model of airway hyperresponsiveness; the adoptive transfer of maDCs, DCregs, and T cells; and T-cell function were studied. Results Antigen-pulsed maDCs inhibited antigen-specific IgE production but enhanced the production of antigen-specific IgG1 and IgG2a. Analysis of Ifng−/− mice and Il21r−/− mice revealed that the inhibitory effect of antigen-pulsed maDCs on antigen-specific IgE production involved IL-21–producing T follicular helper cells but not IFN-γ–producing TH 1 cells. In contrast, antigen-pulsed DCregs impaired the production of antigen-specific IgE, IgG1, and IgG2a. In vivo blockade experiments showed that antigen-specific CD4+ CD25+ Foxp3+ regulatory T cells mainly mediated the suppressive effect of antigen-pulsed DCregs on the production of antigen-specific IgE. Antigen-pulsed maDCs promoted airway inflammation, whereas antigen-pulsed DCregs markedly suppressed the pathogenesis. Conclusion DCregs abolish TH 2-mediated IgE production and allergic inflammation based on antigen-specific dominant tolerance, whereas maDCs exacerbate the pathogenesis despite inhibiting the IgE response through the activation of diverse types of TH cell responses.