PMID- 30068989 OWN - NLM STAT- MEDLINE DCOM- 20191203 LR - 20191203 IS - 2041-4889 (Electronic) VI - 9 IP - 8 DP - 2018 Aug 1 TI - Rsad2 is necessary for mouse dendritic cell maturation via the IRF7-mediated signaling pathway. PG - 823 LID - 10.1038/s41419-018-0889-y [doi] LID - 823 AB - Dendritic cells (DCs) are the most potent professional antigen presenting cells and inducers of T cell-mediated immunity. However, few specific markers of mature DCs (mDC) have been reported. A previous microarray analysis revealed expression of mDC-specific genes and identified Rsad2 (radical S-adenosyl methionine domain containing 2) as a candidate specific marker for DC maturation. Mouse bone marrow-derived DCs were transfected with Rsad2 siRNA and examined by flow cytometry, ELISA, western, and confocal microscopy. C57BL/6 mice received intravenously B16F10 cells to establish a pulmonary metastasis model. Tumor-bearing mice then received subcutaneously two injections of mDCs or Rsad2 knockdown DCs. The cytotoxic T lymphocyte (CTL) population was examined from splenocytes of DC-vaccinated mice by flow cytometry. Rsad2 was induced at high levels in LPS-stimulated mDCs and mDC function was markedly attenuated under conditions of Rsad2 knockdown. Moreover, Rsad2 was necessary for mDC maturation via the IRF7-mediated signaling pathway. The importance of Rsad2 was confirmed in an Rsad2 knockdown lung metastasis mouse model in which mDCs lost their antitumor efficacy. Data on the CTL population further supported the results as above. Taken together, Rsad2 was an obvious and specific marker necessary for DC maturation and these findings will be clearly helpful for further understanding of DC biology. FAU - Jang, Ji-Su AU - Jang JS AD - Department of Biotechnology, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi-do, 13488, Republic of Korea. FAU - Lee, Jun-Ho AU - Lee JH AD - Department of Biotechnology, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi-do, 13488, Republic of Korea. AD - Pharos Vaccine Inc., 545 Dunchon-daero, Jungwon-gu, Seongnam, Gyeonggi-do, 13215, Republic of Korea. FAU - Jung, Nam-Chul AU - Jung NC AD - Pharos Vaccine Inc., 545 Dunchon-daero, Jungwon-gu, Seongnam, Gyeonggi-do, 13215, Republic of Korea. FAU - Choi, So-Yeon AU - Choi SY AD - Department of Biotechnology, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi-do, 13488, Republic of Korea. FAU - Park, Soo-Yeoun AU - Park SY AD - Department of Biotechnology, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi-do, 13488, Republic of Korea. FAU - Yoo, Ji-Young AU - Yoo JY AD - Department of Biotechnology, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi-do, 13488, Republic of Korea. FAU - Song, Jie-Young AU - Song JY AUID- ORCID: 0000-0003-2434-7511 AD - Department of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 01812, Republic of Korea. FAU - Seo, Han Geuk AU - Seo HG AD - Department of Food Science and Biotechnology of Animal Products, Sanghuh College of Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. FAU - Lee, Hyun Soo AU - Lee HS AD - Pharos Vaccine Inc., 545 Dunchon-daero, Jungwon-gu, Seongnam, Gyeonggi-do, 13215, Republic of Korea. FAU - Lim, Dae-Seog AU - Lim DS AD - Department of Biotechnology, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi-do, 13488, Republic of Korea. dslim@cha.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180801 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Interferon Regulatory Factor-7) RN - 0 (Interferon Type I) RN - 0 (Irf7 protein, mouse) RN - 0 (Lipopolysaccharides) RN - 0 (Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (Rsad2 protein, mouse) SB - IM MH - Animals MH - Bone Marrow Cells/cytology MH - Cell Line, Tumor MH - Dendritic Cells/cytology/drug effects/*immunology MH - Interferon Regulatory Factor-7/*metabolism MH - Interferon Type I/metabolism MH - Lipopolysaccharides/pharmacology MH - Lung Neoplasms/immunology/secondary/therapy MH - Male MH - Melanoma, Experimental/metabolism/pathology MH - Mice MH - Mice, Inbred C57BL MH - Proteins/antagonists & inhibitors/genetics/*metabolism MH - RNA Interference MH - RNA, Small Interfering/metabolism MH - Signal Transduction MH - T-Lymphocytes, Cytotoxic/cytology/immunology PMC - PMC6070531 COIS- The authors declare that they have no conflict of interest. EDAT- 2018/08/03 06:00 MHDA- 2019/12/04 06:00 PMCR- 2018/08/01 CRDT- 2018/08/03 06:00 PHST- 2018/06/23 00:00 [received] PHST- 2018/07/17 00:00 [accepted] PHST- 2018/07/17 00:00 [revised] PHST- 2018/08/03 06:00 [entrez] PHST- 2018/08/03 06:00 [pubmed] PHST- 2019/12/04 06:00 [medline] PHST- 2018/08/01 00:00 [pmc-release] AID - 10.1038/s41419-018-0889-y [pii] AID - 889 [pii] AID - 10.1038/s41419-018-0889-y [doi] PST - epublish SO - Cell Death Dis. 2018 Aug 1;9(8):823. doi: 10.1038/s41419-018-0889-y.