Immune Modulation and Tolerance Induction by RelB-Silenced Dendritic Cells through RNA Interference | Zendy

Mu Li | Zendy; Xusheng Zhang | Zendy; Xiufen Zheng | Zendy; Dameng Lian | Zendy; ZhuXu Zhang | Zendy; Weiwen Ge | Zendy; JinMing Yang | Zendy; Costin Vladau | Zendy; Motohiko Suzuki | Zendy; Dong Chen | Zendy; Robert Zhong | Zendy; Bertha García | Zendy; Anthony M. Jevnikar | Zendy; WeiPing Min | Zendy

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Immune Modulation and Tolerance Induction by RelB-Silenced Dendritic Cells through RNA Interference

Author(s) -

Mu Li,

Xusheng Zhang,

Xiufen Zheng,

Dameng Lian,

ZhuXu Zhang,

Weiwen Ge,

JinMing Yang,

Costin Vladau,

Motohiko Suzuki,

Dong Chen,

Robert Zhong,

Bertha García,

Anthony M. Jevnikar,

WeiPing Min

Publication year - 2007

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.178.9.5480

Subject(s) - relb , immune tolerance , immune system , microbiology and biotechnology , cd80 , cd86 , gene silencing , biology , small interfering rna , rna interference , dendritic cell , foxp3 , immunology , chemistry , cancer research , t cell , in vitro , rna , cd40 , transfection , nfkb1 , cytotoxic t cell , cell culture , transcription factor , biochemistry , genetics , gene

Dendritic cells (DC), the most potent APCs, can initiate the immune response or help induce immune tolerance, depending upon their level of maturation. DC maturation is associated with activation of the NF-kappaB pathway, and the primary NF-kappaB protein involved in DC maturation is RelB, which coordinates RelA/p50-mediated DC differentiation. In this study, we show that silencing RelB using small interfering RNA results in arrest of DC maturation with reduced expression of the MHC class II, CD80, and CD86. Functionally, RelB-silenced DC inhibited MLR, and inhibitory effects on alloreactive immune responses were in an Ag-specific fashion. RelB-silenced DC also displayed strong in vivo immune regulation. An inhibited Ag-specific response was seen after immunization with keyhole limpet hemocyanin-pulsed and RelB-silenced DC, due to the expansion of T regulatory cells. Administration of donor-derived RelB-silenced DC significantly prevented allograft rejection in murine heart transplantation. This study demonstrates for the first time that transplant tolerance can be induced by means of RNA interference using in vitro-generated tolerogenic DC.

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