Abstract Background: The mechanisms by which human dendritic cells (DCs) activate a TH1-polarizing or TH2-polarizing program are still partially unclear. Objective: Study of the mechanisms responsible for the TH1/TH2-polarizing activity of human circulating myeloid DCs before and after ligation of their Toll-like receptors (TLRs). Methods: IL-4 and IFN-g production by CD4 T cells was assessed in cocultures with myeloid DCs before or after TLR triggering. Expression of Jagged-1 and Delta-4 Notch ligands and of GATA-3 and T-box expressed in T cells transcription factors was evaluated by real-time quantitative PCR. Signal transducer and activator of transcription 4 and 6 phosphorylation was assessed by flow cytometry. Knockdown of Jagged-1 or Delta-4 was performed by transfection of DCs with appropriate silencing mRNAs. Results: Myeloid immature DCs constitutively expressed Jagged-1, which induces in CD4 T cells a TH2 polarization, as shown by Jagged-1 gene silencing. The TH2 polarization associated with high GATA-3/T-box expressed in T cells ratio and was at least partially dependent on the early induction of IL-4. Maturation of DCs by TLR ligation resulted in the reduction of Jagged-1 and upregulation of Delta-4, which was at least in part responsible for the polarization of CD4 T cells to the TH1 phenotype. Conclusion: CD4 T-cell responses are usually characterized by a prevalent TH2 phenotype unless TLRs are triggered on DCs by microbial components. (J Allergy Clin Immunol 2008;121:1000-5.)

Human immature myeloid dendritic cells trigger a TH2-polarizing program via Jagged-1/Notch interaction / F. LIOTTA; F. FROSALI; V. QUERCI; A. MANTEI; L. FILÌ; L. MAGGI; B. MAZZINGHI; R. ANGELI; E. RONCONI; V. SANTARLASCI; T. BIAGIOLI; L. LASAGNI; C. BALLERINI; P. PARRONCHI; A. SCHEFFOLD; L. COSMI; E. MAGGI; S. ROMAGNANI; F. ANNUNZIATO. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. - ISSN 0091-6749. - STAMPA. - 21:(2008), pp. 1000-1008. [10.1016/j.jaci.2008.01.004]

Human immature myeloid dendritic cells trigger a TH2-polarizing program via Jagged-1/Notch interaction.

LIOTTA, FRANCESCO;FROSALI, FRANCESCA;FILI', LUCIA;MAGGI, LAURA;MAZZINGHI, BENEDETTA;ANGELI, ROBERTA;RONCONI, ELISA;SANTARLASCI, VERONICA;LASAGNI, LAURA;BALLERINI, CLARA;PARRONCHI, PAOLA;COSMI, LORENZO;MAGGI, ENRICO;ROMAGNANI, SERGIO;ANNUNZIATO, FRANCESCO
2008

Abstract

Abstract Background: The mechanisms by which human dendritic cells (DCs) activate a TH1-polarizing or TH2-polarizing program are still partially unclear. Objective: Study of the mechanisms responsible for the TH1/TH2-polarizing activity of human circulating myeloid DCs before and after ligation of their Toll-like receptors (TLRs). Methods: IL-4 and IFN-g production by CD4 T cells was assessed in cocultures with myeloid DCs before or after TLR triggering. Expression of Jagged-1 and Delta-4 Notch ligands and of GATA-3 and T-box expressed in T cells transcription factors was evaluated by real-time quantitative PCR. Signal transducer and activator of transcription 4 and 6 phosphorylation was assessed by flow cytometry. Knockdown of Jagged-1 or Delta-4 was performed by transfection of DCs with appropriate silencing mRNAs. Results: Myeloid immature DCs constitutively expressed Jagged-1, which induces in CD4 T cells a TH2 polarization, as shown by Jagged-1 gene silencing. The TH2 polarization associated with high GATA-3/T-box expressed in T cells ratio and was at least partially dependent on the early induction of IL-4. Maturation of DCs by TLR ligation resulted in the reduction of Jagged-1 and upregulation of Delta-4, which was at least in part responsible for the polarization of CD4 T cells to the TH1 phenotype. Conclusion: CD4 T-cell responses are usually characterized by a prevalent TH2 phenotype unless TLRs are triggered on DCs by microbial components. (J Allergy Clin Immunol 2008;121:1000-5.)
2008
21
1000
1008
F. LIOTTA; F. FROSALI; V. QUERCI; A. MANTEI; L. FILÌ; L. MAGGI; B. MAZZINGHI; R. ANGELI; E. RONCONI; V. SANTARLASCI; T. BIAGIOLI; L. LASAGNI; C. BALLERINI; P. PARRONCHI; A. SCHEFFOLD; L. COSMI; E. MAGGI; S. ROMAGNANI; F. ANNUNZIATO
File in questo prodotto:
File Dimensione Formato  
Liotta JACI 2008.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Tutti i diritti riservati
Dimensione 869.3 kB
Formato Adobe PDF
869.3 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/333917
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 61
  • ???jsp.display-item.citation.isi??? 53
social impact