Silencing invariant chain of DCs enhances Th1 response using small interfering RNA.
RNA interference (RNAi), which causes the degradation of any RNA in a sequence specific manner, is a posttranscriptional gene silencing mechanism. Targeting the invariant chain (Ii) in DCs has been used as an approach to enhance antitumor immunity. It is demonstrated in this article that transfection of H-2(K) DCs with siRNA specific for Ii gene can significantly knock down Ii. When exposed to TNF-alpha, immature DCs transfected with Ii siRNA can differentiate into mature DCs without reducing viability or IL-12p70 production. Ii siRNA-treated H-2(K) DCs exhibited an increased allostimulatory capacity in a lymphocyte proliferation assay. Furthermore, Ii siRNA-transfected H-2(K) DCs enhanced Th1 responses by increasing IFN-gamma and decreasing IL-4 production, and much stronger cytotoxic activity was observed when DCs were co-transfected with Ii siRNA and an endogenous tumor antigen in vitro. Our findings indicate that silencing the Ii gene in DCs with siRNA may offer a potential approach to enhancing antitumor immunotherapy.
Ke
Shan
S
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200025, PR China.
Chen
Xue-Hua
XH
Li
Hao
H
Li
Jian-Fang
JF
Gu
Qin-Long
QL
Liu
Bing-Ya
BY
Zhu
Zheng-Gang
ZG
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D034741:RNA, Small Interfering; C045084:invariant chain; D018664:Interleukin-12