title: Silencing c-Kit expression in human DCs suppresses Th2, Th17 response but enhances Th1 response.
abstract: Dendritic cells (DCs) are integral to the differentiation of T helper cells into T helper type 1 TH1, TH2 and TH17 subsets. RNA interference (RNAi), which causes the degradation of any RNA in a sequence specific manner, is a posttranscriptional gene silencing mechanism. Targeting the c-Kit in DCs has been used as an approach to enhance antitumor immunity. Here, we shwed that transfection of DCs with siRNA specific for c-Kit gene can significantly knock down c-Kit. When exposed to TNF-α, immature DCs transfected with c-Kit siRNA can differentiate into mature DCs without reducing viability or IL-12p70 production. The c-Kit siRNA-treated DCs exhibited an increased allostimulatory capacity in a lymphocyte proliferation assay. Furthermore, c-Kit siRNA-transfected DCs enhanced TH1 responses by increasing IFN-γ and decreasing IL-4 production, and much stronger cytotoxic activity was observed when DCs were co-transfected with c-Kit siRNA and an endogenous tumor antigen in vitro. Our findings indicate that silencing the c-Kit gene in DCs with siRNA may offer a potential approach to enhance antitumor immunotherapy.
authors.affiliation: Department of Dermatology, Wuhan General Hospital of Guangzhou Command Wuluo Road 627, Wuhan 430070, Hubei Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Medical Laboratory, Wuhan General Hospital of Guangzhou Command Wuluo Road 627, Wuhan 430070, Hubei Province, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Medical Laboratory, Wuhan General Hospital of Guangzhou Command Wuluo Road 627, Wuhan 430070, Hubei Province, China.
authors.forename: Qianchuan
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Dermatology, Wuhan General Hospital of Guangzhou Command Wuluo Road 627, Wuhan 430070, Hubei Province, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Dermatology, Wuhan General Hospital of Guangzhou Command Wuluo Road 627, Wuhan 430070, Hubei Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Dermatology, Wuhan General Hospital of Guangzhou Command Wuluo Road 627, Wuhan 430070, Hubei Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tong
keywords: Small interfering RNA; anti-tumor immunity; c-Kit; dendritic cells