PMID- 32681834 OWN - NLM STAT- MEDLINE DCOM- 20210811 LR - 20211105 IS - 1525-0024 (Electronic) IS - 1525-0016 (Print) IS - 1525-0016 (Linking) VI - 28 IP - 11 DP - 2020 Nov 4 TI - Circular RNA circSnx5 Controls Immunogenicity of Dendritic Cells through the miR-544/SOCS1 Axis and PU.1 Activity Regulation. PG - 2503-2518 LID - S1525-0016(20)30352-X [pii] LID - 10.1016/j.ymthe.2020.07.001 [doi] AB - Dendritic cells (DCs) can orchestrate either immunogenic or tolerogenic responses to relay information on the functional state. Emerging studies indicate that circular RNAs (circRNAs) are involved in immunity; however, it remains unclear whether they govern DC development and function at the transcriptional level. In this study, we identified a central role for a novel circRNA, circSnx5, in modulating DC-driven immunity and tolerance. Ectopic circSnx5 suppresses DC activation and promotes the development of tolerogenic functions of DCs, while circSnx5 knockdown promotes their activation and inflammatory phenotype. Mechanistically, circSnx5 can act as a miR-544 sponge to attenuate miRNA-mediated target depression on suppressor of cytokine signaling 1 (SOCS1) and inhibit nuclear translocation of PU.1, regulating DC activation and function. Furthermore, the main splicing factors (SFs) were identified in DCs, of which heterogeneous nuclear ribonucleoprotein (hnRNP) C was essential for circSnx5 generation. Moreover, our data demonstrated that vaccination with circSnx5-conditioned DCs prolonged cardiac allograft survival in mice and alleviated experimental autoimmune myocarditis. Taken together, our results revealed circSnx5 as a key modulator to fine-tune DC function, suggesting that circSnx5 may serve as a potential therapeutic avenue for immune-related diseases. CI - Copyright (c) 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved. FAU - Chen, Qi AU - Chen Q AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Mang, Ge AU - Mang G AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Wu, Jian AU - Wu J AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Sun, Ping AU - Sun P AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Li, Tingting AU - Li T AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Zhang, Hanlu AU - Zhang H AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Wang, Naixin AU - Wang N AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Tong, Zhonghua AU - Tong Z AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Wang, Weiwei AU - Wang W AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Zheng, Yang AU - Zheng Y AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - Tian, Jinwei AU - Tian J AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. FAU - E, Mingyan AU - E M AD - Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin 50001, Heilongjiang Province, China. Electronic address: emingyan889@163.com. FAU - Zhang, Maomao AU - Zhang M AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. Electronic address: maomaolp1983@163.com. FAU - Yu, Bo AU - Yu B AD - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150001, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 50001, Heilongjiang Province, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200703 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 RN - 0 (Heterogeneous-Nuclear Ribonucleoproteins) RN - 0 (MIRN-544 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Circular) RN - 0 (SNX5 protein, human) RN - 0 (Socs1 protein, mouse) RN - 0 (Sorting Nexins) RN - 0 (Suppressor of Cytokine Signaling 1 Protein) RN - 0 (Trans-Activators) RN - 0 (proto-oncogene protein Spi-1) SB - IM MH - Animals MH - Dendritic Cells/*immunology/*metabolism MH - *Gene Expression Regulation MH - Heterogeneous-Nuclear Ribonucleoproteins/metabolism MH - Immune Tolerance MH - Immunity MH - Immunomodulation/genetics MH - Mice MH - Mice, Knockout MH - MicroRNAs/*genetics MH - Proto-Oncogene Proteins/genetics/metabolism MH - *RNA, Circular MH - Sorting Nexins/*genetics MH - Suppressor of Cytokine Signaling 1 Protein/*genetics MH - Trans-Activators/genetics/metabolism PMC - PMC7646215 OTO - NOTNLM OT - circSnx5 OT - circular RNA OT - dendritic cell OT - immunity EDAT- 2020/07/19 06:00 MHDA- 2021/08/12 06:00 PMCR- 2021/11/04 CRDT- 2020/07/19 06:00 PHST- 2019/11/06 00:00 [received] PHST- 2020/05/13 00:00 [revised] PHST- 2020/06/28 00:00 [accepted] PHST- 2020/07/19 06:00 [pubmed] PHST- 2021/08/12 06:00 [medline] PHST- 2020/07/19 06:00 [entrez] PHST- 2021/11/04 00:00 [pmc-release] AID - S1525-0016(20)30352-X [pii] AID - 10.1016/j.ymthe.2020.07.001 [doi] PST - ppublish SO - Mol Ther. 2020 Nov 4;28(11):2503-2518. doi: 10.1016/j.ymthe.2020.07.001. Epub 2020 Jul 3.