PMID- 28578354 OWN - NLM STAT- MEDLINE DCOM- 20170804 LR - 20220331 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 42 IP - 2 DP - 2017 TI - Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model. PG - 455-468 LID - 10.1159/000477593 [doi] AB - BACKGROUND/AIMS: Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance. METHODS & RESULTS: We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression. Functionally, such cells showed a significantly enhanced migration rate in the chemotactic assay and decreased T-cell proliferation after lipopolysaccharide stimulation in mixed lymphocyte reactions. Cotransfected cells showed an increased ability to induce immune tolerance by upregulating T regulatory (Treg) cells and shifting the Th1/Th2 ratio. Cotransfection of Ad-CCR7 and RelB-siRNA endowed imDCs with resistance to apoptosis and cell death. CCR7 overexpression and RelB knockdown (KD) in imDCs improve skin-graft survival in a murine skin-transplantation model. CONCLUSION: Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection. CI - (c) 2017 The Author(s). Published by S. Karger AG, Basel. FAU - Dong, Zhiwei AU - Dong Z AD - Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China. FAU - Chen, Yajie AU - Chen Y AD - Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China. FAU - Peng, Yuan AU - Peng Y AD - The first clinical college of Chongqing Medical University, Chongqing, China. FAU - Wang, Fan AU - Wang F AD - Department of Plastic and Reconstructive Surgery of Southwest Hospital, Third Military Medical University Chongqing, Chongqing, China. FAU - Yang, Zichen AU - Yang Z AD - Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China. FAU - Huang, Guangtao AU - Huang G AD - Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China. FAU - Chen, Yu AU - Chen Y AD - Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China. FAU - Yuan, Zhiqiang AU - Yuan Z AD - Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China. FAU - Cao, Tongtong AU - Cao T AD - Department of Pathology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Peng, Yizhi AU - Peng Y AD - Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China. LA - eng PT - Journal Article DEP - 20170605 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Ccr7 protein, mouse) RN - 0 (Receptors, CCR7) RN - 0 (Relb protein, mouse) RN - 147337-75-5 (Transcription Factor RelB) SB - IM MH - Adenoviridae MH - Animals MH - Dendritic Cells/immunology/metabolism MH - Gene Expression Regulation MH - Graft Rejection/genetics/immunology MH - Graft Survival/genetics MH - Humans MH - Immune Tolerance/*genetics MH - Mice MH - Receptors, CCR7/*biosynthesis/genetics MH - Skin/*immunology/metabolism MH - T-Lymphocytes, Regulatory/immunology/metabolism MH - Transcription Factor RelB/*genetics MH - Transfection OTO - NOTNLM OT - CCR7 OT - Immune tolerance OT - RelB OT - Transplantation OT - Treg cells OT - imDCs EDAT- 2017/06/05 06:00 MHDA- 2017/08/05 06:00 CRDT- 2017/06/05 06:00 PHST- 2016/12/12 00:00 [received] PHST- 2017/03/28 00:00 [accepted] PHST- 2017/06/05 06:00 [pubmed] PHST- 2017/08/05 06:00 [medline] PHST- 2017/06/05 06:00 [entrez] AID - 000477593 [pii] AID - 10.1159/000477593 [doi] PST - ppublish SO - Cell Physiol Biochem. 2017;42(2):455-468. doi: 10.1159/000477593. Epub 2017 Jun 5.