title: Dermatophagoides pteronyssinus group 2 allergen bound to 8-OH modified adenine reduces the Th2-mediated airway inflammation without inducing a Th17 response and autoimmunity.
abstract: 8-OH modified adenine bound to Dermatophagoides pteronyssinus group 2 (nDer p2-Conj), a novel allergen-TLR7 agonist conjugate, improves murine airway inflammation in priming and therapeutic settings, however no data are known on the activity of this construct on Th17 cells. The aim of the study was to evaluate if nDer p2-Conj elicited in vivo Th17 cells and Th17-driven autoimmune responses, by using both short- and long-term priming and therapeutic protocols in a nDer p2-driven model of murine airway inflammation. The conjugate induced the in vitro production of cytokines favouring the Th17 polarization by bone marrow-derived dendritic cells. In short-term protocols, the priming or treatment with the conjugate ameliorated the airway inflammation by shifting Th2 allergen-specific cells into T cells producing IFN-γ, IL-10, but not IL-17A. Similar results were found in long-term protocol where the conjugate down-regulated airway inflammation without any evidence of autoimmune response and B cell compartment expansion. nDer p2-Conj also failed to shorten the spontaneous onset of diabetes on conjugates-primed NOD/LtJ mice. We found that neutrophils in BALF, ROR-γt and IL-17A expression in lungs were increased in conjugate-treated IL-10KO mice. These data emphasize the role of conjugate-driven IL-10 production, which can regulate the activity of memory Th17 cells and prevent the onset of autoimmune response.
authors.affiliation: Dept. of Experimental and Clinical Medicine, Research Center DENOTHE of University of Florence, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pratesi
authors.affiliation: Dept. of Experimental and Clinical Medicine, Research Center DENOTHE of University of Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nencini
authors.affiliation: Dept. of Experimental and Clinical Medicine, Research Center DENOTHE of University of Florence, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Filì
authors.affiliation: Dept. of Chemistry 'Ugo Schiff', University of Florence, Italy.
authors.forename: Ernesto G
authors.initials: EG
authors.lastname: Occhiato
authors.affiliation: Dept. of Experimental and Clinical Medicine, Research Center DENOTHE of University of Florence, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Romagnani
authors.affiliation: Dept. of Experimental and Clinical Medicine, Research Center DENOTHE of University of Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Parronchi
authors.affiliation: Dept. of Experimental and Clinical Medicine, Research Center DENOTHE of University of Florence, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Maggi
authors.affiliation: Immunoallergology Unit, Dept. of Biomedicine, Careggi Hospital, Florence, Italy. Electronic address: enrico.maggi@unifi.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vultaggio
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology* / Q000494:pharmacology; D060829:Arthropod Proteins / Q000276:immunology* / Q000494:pharmacology; D040002:Dermatophagoides pteronyssinus; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018796:Immunoconjugates / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451163:Dermatophagoides pteronyssinus antigen p 2; D018796:Immunoconjugates; C036009:8-oxoadenosine; D000241:Adenosine
keywords: Adenine-derivatives; Adjuvants; Immunotherapy; Toll-like receptors; Vaccines