Dermatophagoides pteronyssinus group 2 allergen bound to 8-OH modified adenine reduces the Th2-mediated airway inflammation without inducing a Th17 response and autoimmunity. (September 2016)

• Record Type: Journal Article
• Authors: Pratesi, Sara; Nencini, Francesca; Filì, Lucia; Occhiato, Ernesto G.; Romagnani, Sergio; Parronchi, Paola; Maggi, Enrico; Vultaggio, Alessandra
• Is Part Of: Molecular immunology. Volume 77(2016:Sep.)
• Page Start: 60
• Page End: 70
• Publication Date: 2016-09
• Subjects: AIT allergy immunotherapy -- BALF bronchoalveolar lavage fluid -- BMDC bone marrow dendritic cell -- DC dendritic cell -- i.t. intratracheally -- MNC mononuclear cells -- nDer p2 natural dermatophagoides pteronyssinus group 2 major allerg; Adjuvants -- Vaccines -- Toll-like receptors -- Adenine-derivatives -- Immunotherapy; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2016.07.011
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: 8-OH modified adenine bound to Dermatophagoides pteronyssinus group 2 a novel allergen-TLR7 agonist conjugate, ameliorated the murine airway inflammation. The conjugate induced the shifting of Th2 cells into Th1/Tr1 cells producing IFN-γ, IL-10, but not IL-17A, in a nDer p2-driven model of airway inflammation by using both priming and therapeutic protocol. The conjugate induced pro-Th17 cytokines by BMDC, but the IL-10 upregulation was able to block Th17 cell development. The conjugate did not promote autoimmune response with B cell expansion and production of autoantibodies in a long-term protocol of airway inflammation. The conjugate represents a novel and safe adjuvant for immunotherapy. 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.