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PI16 is expressed by a subset of human memory Treg with enhanced migration to CCL17 and CCL20
Authors:Nicholson Ian C  Mavrangelos Christos  Bird Daniel R G  Bresatz-Atkins Suzanne  Eastaff-Leung Nicola G  Grose Randall H  Gundsambuu Batjargal  Hill Danika  Millard Debbrah J  Sadlon Timothy J  To Sarah  Zola Heddy  Barry Simon C  Krumbiegel Doreen
Affiliation:Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China.
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.
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