Tolerogenic dendritic cells generated by RelB silencing using shRNA prevent acute rejection.
Abstract
It is well known that adoptive transfer of donor-derived tolerogenic dendritic cells (DCs) helps to induce immune tolerance. RelB, one of NF-κB subunits, is a critical element involved in DC maturation. In the present study, our results showed tolerogenic DCs could be acquired via silencing RelB using small interfering RNA. Compared with imDCs, the tolerogenic DCs had more potent ability to inhibit mixed lymphocyte reaction (MLR) and down-regulate Th1 cytokines and prompt the production of Th2 cytokines. They both mediated immune tolerance via the increased of T cell apoptosis and generation of regulatory T cells. Administration of donor-derived tolerogenic DCs significantly prevented the allograft rejection and prolonged the survival time in a murine heart transplantation model. Our results demonstrate donor-derived, RelB-shRNA induced tolerogenic DCs can significantly induce immune tolerance in vitro and in vivo.
Links
Authors
Zhu HC, Qiu T, Liu XH, Dong WC, Weng XD, Hu CH, Kuang YL, Gao RH, Dan C, Tao T
Institution
Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China.
Source
Cellular immunology 274:1-2 2012 pg 12-8MeSH
Adoptive TransferAnimals
Apoptosis
Cytokines
Dendritic Cells
Graft Rejection
Graft Survival
Heart Transplantation
Immune Tolerance
Lymphocyte Culture Test, Mixed
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
RNA Interference
RNA, Small Interfering
T-Lymphocytes, Regulatory
Th1 Cells
Th2 Cells
Transcription Factor RelB
Pub Type(s)
Journal ArticleResearch Support, Non-U.S. Gov't
Language
eng
PubMed ID
22464914
Log In

