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Hum Vaccin Immunother. 2013 Oct;9(10):2237-45. doi: 10.4161/hv.25011. Epub 2013 Jun 4.

DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals.

Author information

  • 1Key laboratory of Medical Molecular Virology of MOE and MOH; Fudan University Shanghai Medical College; Shanghai, P.R. China.
  • 2Department of Experimental Therapeutics; Division of Cancer Medicine; The University of Texas M.D. Anderson Cancer Center; Houston, TX USA.
  • 3State Key Laboratory for Agro-Biotechnology; Department of Microbiology and Immunology; College of Biological Science; China Agricultural University; Beijing, P.R. China.
  • 4Key laboratory of Medical Molecular Virology of MOE and MOH; Fudan University Shanghai Medical College; Shanghai, P.R. China; State Key Laboratory for Agro-Biotechnology; Department of Microbiology and Immunology; College of Biological Science; China Agricultural University; Beijing, P.R. China.

Abstract

We previously demonstrated that DNA and protein co-administration induced differentiation of immature dendritic cells (iDCs) into CD11c(+)CD40(low)IL-10(+) regulatory DCs (DCregs) via the caveolin-1 (Cav-1) -mediated signal pathway. Here, we demonstrate that production of IL-10 and the low expression of CD40 play a critical role in the subsequent induction of regulatory T cells (Tregs) by the DCregs. We observed that DNA and protein were co-localized with DC-SIGN in caveolae and early lysosomes in the treated DCs, as indicated by co-localization with Cav-1 and EEA-1 compartment markers. DNA and protein also co-localized with LAMP-2. Gene-array analysis of gene expression showed that more than a thousand genes were significantly changed by the DC co-treatment with DNA + protein compared with controls. Notably, the level of DC-SIGN expression was dramatically upregulated in pOVA + OVA co-treated DCs. The expression levels of Rho and Rho GNEF, the down-stream molecules of DC-SIGN mediated signal pathway, were also greatly upregulated. Further, the level of TLR9, the traditional DNA receptor, was significantly downregulated. These results suggest that DC-SIGN as the potential receptor for DNA and protein might trigger the negative pathway to contribute the induction of DCreg combining with Cav-1 mediated negative signal pathway.

KEYWORDS:

DC-SIGN; DNA and protein co-administration; cavelin-1; iTreg; tolerance

PMID:
24051433
[PubMed - in process]
PMCID:
PMC3906410
Free PMC Article

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