Background: As the new TLR/-ligand 8-hydroxyadenine SA-2 was found by our group torevert allergen specific TH2 responses both in vitro and in vivo, we studied a new compuond able to be coupled with allergenic molecules as a possible new adjuvant for possible application in allergen-specific immunotherapy. Methods: THE 8-oh-substituted adenine SA-26e chemically coupled with Dermatophagoides Pteronissinus extract (DP-conj) or purified natural Der p2 (nDer p2-Conj) was evaluated for induction of NF-kB in CD14+ cells, cytokine production in BDCA4+ and CD14+ cells, Th-skewing effects in allergen-specific human T cell lines, TLR-triggering in transfected HEK293 cell line. Results: Both DP-Conj and nDer-Conj induced innate cells to produce IFN-alfa and IL-12. As a consequence, the two conjugates reverted TH2-prone allergen T cell lines into IFN-gamma-producing cells (TH1/TH0 phenotype) as assessed by cytokine production in the supernatants, intracellular cytokine expression and TH-related transcription factor expression. DP-Conj and nDer-Conj induced nuclear translocation of p50 and trigger TLR7. Conclusions: 8-hydroxy-adenines represent new compounds inducing NF-kB translocation and exhibiting TH1-inducing activity in vitro. A system of chemical conjugation to relevant proteins as allergens has been set up with maintenance of modulatory effects of these complexes thus allowing the development of new vaccine strategies.

A modified adenine chemically coupled to allergenic molecule(s) as inducer of allergen-specific Th2 cells redirection / L. Filì; E. Cardilicchia; A. Casini; L. Maggi; C. Manuelli; F. Annunziato; E. Occhiato; E. Maggi; S. Romagnani; P. Parronchi. - STAMPA. - (2011), pp. 219-219. ((Intervento presentato al convegno TOLL 2011, decoding Innate Immunity tenutosi a Riva del Garda (Italy) nel May 4-7 2011.

A modified adenine chemically coupled to allergenic molecule(s) as inducer of allergen-specific Th2 cells redirection

FILI', LUCIA;CARDILICCHIA, ELISA;MAGGI, LAURA;MANUELLI, CINZIA;ANNUNZIATO, FRANCESCO;OCCHIATO, ERNESTO GIOVANNI;MAGGI, ENRICO;ROMAGNANI, SERGIO;PARRONCHI, PAOLA
2011

Abstract

Background: As the new TLR/-ligand 8-hydroxyadenine SA-2 was found by our group torevert allergen specific TH2 responses both in vitro and in vivo, we studied a new compuond able to be coupled with allergenic molecules as a possible new adjuvant for possible application in allergen-specific immunotherapy. Methods: THE 8-oh-substituted adenine SA-26e chemically coupled with Dermatophagoides Pteronissinus extract (DP-conj) or purified natural Der p2 (nDer p2-Conj) was evaluated for induction of NF-kB in CD14+ cells, cytokine production in BDCA4+ and CD14+ cells, Th-skewing effects in allergen-specific human T cell lines, TLR-triggering in transfected HEK293 cell line. Results: Both DP-Conj and nDer-Conj induced innate cells to produce IFN-alfa and IL-12. As a consequence, the two conjugates reverted TH2-prone allergen T cell lines into IFN-gamma-producing cells (TH1/TH0 phenotype) as assessed by cytokine production in the supernatants, intracellular cytokine expression and TH-related transcription factor expression. DP-Conj and nDer-Conj induced nuclear translocation of p50 and trigger TLR7. Conclusions: 8-hydroxy-adenines represent new compounds inducing NF-kB translocation and exhibiting TH1-inducing activity in vitro. A system of chemical conjugation to relevant proteins as allergens has been set up with maintenance of modulatory effects of these complexes thus allowing the development of new vaccine strategies.
TOLL 2011
TOLL 2011, decoding Innate Immunity
Riva del Garda (Italy)
May 4-7 2011
L. Filì; E. Cardilicchia; A. Casini; L. Maggi; C. Manuelli; F. Annunziato; E. Occhiato; E. Maggi; S. Romagnani; P. Parronchi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/977400
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