DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals.
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.
Key laboratory of Medical Molecular Virology of MOE and MOH; Fudan University Shanghai Medical College; Shanghai, P.R. China.
Jinyao
J
Li
Key laboratory of Medical Molecular Virology of MOE and MOH; Fudan University Shanghai Medical College; Shanghai, P.R. China.
Shuang
S
Geng
Department of Experimental Therapeutics; Division of Cancer Medicine; The University of Texas M.D. Anderson Cancer Center; Houston, TX USA.
Xiuping
X
Liu
State Key Laboratory for Agro-Biotechnology; Department of Microbiology and Immunology; College of Biological Science; China Agricultural University; Beijing, P.R. China.
Hu
H
Liu
State Key Laboratory for Agro-Biotechnology; Department of Microbiology and Immunology; College of Biological Science; China Agricultural University; Beijing, P.R. China.
Huali
H
Jin
Department of Experimental Therapeutics; Division of Cancer Medicine; The University of Texas M.D. Anderson Cancer Center; Houston, TX USA.
Chang-Gong
CG
Liu
Key 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.
Bin
B
Wang
D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D007108:Immune Tolerance; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000008:administration & dosage / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D004247:DNA; D037181:Lectins, C-Type; D011506:Proteins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
DC-SIGN; DNA and protein co-administration; cavelin-1; iTreg; tolerance