Treatment with 8-OH-modified adenine (TLR7 ligand)-allergen conjugates decreases T helper type 2-oriented murine airway inflammation.
A strategy to improve allergen-specific immunotherapy is to employ new adjuvants stably linked to allergens. The study is addressed to evaluate the in vivo and in vitro effects of allergens [natural Dermatophagoides pteronyssinus 2 (nDer p 2) and ovalbumin (OVA)] chemically bound to an 8-OH-modified adenine. Humoral and cellular responses were analysed in allergen-sensitized and challenged mice by using conjugates (Conj) in a therapeutic setting. The in vitro activity of the conjugates on cytokine production induced by bone marrow dendritic cells and the co-culture system was also investigated. The nDer p 2-Conj treatment in nDer p 2-primed and challenged BALB/c mice reduced the numbers of eosinophils in bronchoalveolar lavage fluid and lung, airway allergen-driven interleukin-13 (IL-13) production in lung mononuclear cells and IgE, in comparison with nDer p 2-treated mice. The increase of IgG2a paralleled that of interferon-γ (IFN-γ) and IL-10 in allergen-stimulated spleen cells. Similar effects were elicited by treatment with OVA-Conj in an OVA-driven BALB/c model. The nDer p 2-Conj or OVA-Conj redirected memory T helper type 2 cells towards the production of IL-10 and IFN-γ also in C57BL/6 mice and when subcutaneously administered. Interleukin-10, IL-12 and IL-27 were produced in vitro by Conj-stimulated bone marrow dendritic cells, whereas IL-10 and IFN-γ were up-regulated in co-cultures of CD11c(+) and CD4(+) T cells from Conj-treated mice stimulated with allergen. Cytofluorometric analysis indicated that the Conj expanded IFN-γ- and IL-10- producing memory T cells. The Conj effects on IL-10(-/-) and IL-12(-/-) mice confirmed the role of IL-10 and IFN-γ in inducing a protective and balanced redirection the T helper type 2-mediated airway inflammation.
Department of Experimental and Clinical Medicine, Centre for Research, Transfer and High Education DENOTHE, Florence, Italy.
Francesca
F
Nencini
Department of Experimental and Clinical Medicine, Centre for Research, Transfer and High Education DENOTHE, Florence, Italy.
Sara
S
Pratesi
Department of Experimental and Clinical Medicine, Centre for Research, Transfer and High Education DENOTHE, Florence, Italy.
Giulia
G
Petroni
Department of Experimental and Clinical Medicine, Centre for Research, Transfer and High Education DENOTHE, Florence, Italy.
Lucia
L
Filì
Department of Experimental and Clinical Medicine, Centre for Research, Transfer and High Education DENOTHE, Florence, Italy.
Elisa
E
Cardilicchia
Department of Chemistry 'Ugo Schiff', University of Florence, Florence, Italy.
Andrea
A
Casini
Department of Chemistry 'Ugo Schiff', University of Florence, Florence, Italy.
Ernesto Giovanni
EG
Occhiato
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Laura
L
Calosi
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Daniele
D
Bani
Department of Experimental and Clinical Medicine, Centre for Research, Transfer and High Education DENOTHE, Florence, Italy.
Sergio
S
Romagnani
Department of Experimental and Clinical Medicine, Centre for Research, Transfer and High Education DENOTHE, Florence, Italy.
Enrico
E
Maggi
Department of Experimental and Clinical Medicine, Centre for Research, Transfer and High Education DENOTHE, Florence, Italy.
Paola
P
Parronchi
Immunoallergology Unit, Department of Biomedicine, Careggi Hospital, Florence, Italy.
Alessandra
A
Vultaggio
D000225:Adenine / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology*; D000485:Allergens / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000494:pharmacology*; D060829:Arthropod Proteins / Q000276:immunology / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D018893:Bronchoalveolar Lavage; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000235:genetics / Q000276:immunology
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; C451163:Dermatophagoides pteronyssinus antigen p 2; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D000225:Adenine
adenine derivatives; adjuvants; immunotherapy; toll-like receptors; vaccines