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Treatment with 8‐ OH ‐modified adenine ( TLR 7 ligand)‐allergen conjugates decreases T helper type 2‐oriented murine airway inflammation
Author(s) -
Nencini Francesca,
Pratesi Sara,
Petroni Giulia,
Filì Lucia,
Cardilicchia Elisa,
Casini Andrea,
Occhiato Ernesto Giovanni,
Calosi Laura,
Bani Daniele,
Romagnani Sergio,
Maggi Enrico,
Parronchi Paola,
Vultaggio Alessandra
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12475
Subject(s) - ovalbumin , immunology , cytokine , bone marrow , chemistry , biology , antigen , microbiology and biotechnology
Summary 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 ( nD er 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 nD er p 2‐Conj treatment in nD er 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 nD er 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 nD er 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 CD 11c + and CD 4 + 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.