PMID- 20435931
OWN - NLM
STAT- MEDLINE
DCOM- 20100614
LR  - 20171116
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 184
IP  - 11
DP  - 2010 Jun 1
TI  - Treatment of autoimmune arthritis using RNA interference-modulated dendritic 
      cells.
PG  - 6457-64
LID - 10.4049/jimmunol.0901717 [doi]
AB  - Dendritic cells (DCs) have a dual ability to either stimulate or suppress 
      immunity, which is primarily associated with the expression of costimulatory 
      molecules. Ag-loaded DCs have shown encouraging clinical results for treating 
      cancer and infectious diseases; however, the use of these cells as a means of 
      suppressing immune responses is only recently being explored. Here, we describe 
      the induction of RNA interference through administering short interfering RNA 
      (siRNA) as a means of specifically generating tolerogenic DCs. Knockdown of CD40, 
      CD80, and CD86, prior to loading DCs with the arthritogenic Ag collagen II, led 
      to a population of cells that could effectively suppress onset of 
      collagen-induced arthritis. Maximum benefits were observed when all three genes 
      were concurrently silenced. Disease suppression was associated with inhibition of 
      collagen II-specific Ab production and suppression of T cell recall responses. 
      Downregulation of IL-2, IFN-gamma, TNF-alpha, and IL-17 and increased FoxP3(+) 
      cells with regulatory activity were observed in collagen-induced arthritis mice 
      treated with siRNA-transfected DCs. Collectively, these data support the use of 
      ex vivo gene manipulation in DCs using siRNA to generate tailor-made tolerogenic 
      vaccines for treating autoimmunity.
FAU - Zheng, Xiufen
AU  - Zheng X
AD  - Department of Surgery, University of Western Ontario, Ontario, Canada.
FAU - Suzuki, Motohiko
AU  - Suzuki M
FAU - Ichim, Thomas E
AU  - Ichim TE
FAU - Zhang, Xusheng
AU  - Zhang X
FAU - Sun, Hongtao
AU  - Sun H
FAU - Zhu, Fei
AU  - Zhu F
FAU - Shunnar, Aminah
AU  - Shunnar A
FAU - Garcia, Bertha
AU  - Garcia B
FAU - Inman, Robert D
AU  - Inman RD
FAU - Min, Weiping
AU  - Min W
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100430
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD40 Antigens)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/immunology/*therapy
MH  - Arthritis, Rheumatoid/immunology/therapy
MH  - B7-1 Antigen/genetics
MH  - B7-2 Antigen/genetics
MH  - CD40 Antigens/genetics
MH  - Cell Differentiation/immunology
MH  - Cell Separation
MH  - Dendritic Cells/immunology/*transplantation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Immunotherapy/*methods
MH  - Lymphocyte Activation/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred DBA
MH  - RNA Interference/*immunology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocyte Subsets/immunology
MH  - T-Lymphocytes/immunology
MH  - Transfection
EDAT- 2010/05/04 06:00
MHDA- 2010/06/15 06:00
CRDT- 2010/05/04 06:00
PHST- 2010/05/04 06:00 [entrez]
PHST- 2010/05/04 06:00 [pubmed]
PHST- 2010/06/15 06:00 [medline]
AID - jimmunol.0901717 [pii]
AID - 10.4049/jimmunol.0901717 [doi]
PST - ppublish
SO  - J Immunol. 2010 Jun 1;184(11):6457-64. doi: 10.4049/jimmunol.0901717. Epub 2010 
      Apr 30.