title: Suppressive oligodeoxynucleotides induced tolerogenic plasmacytoid dendritic cells and ameliorated the experimental autoimmune neuritis.
abstract: Toll-like receptor (TLR) 9, recognizing different ligands, confers distinct features of plasmacytoid dendritic cells (pDCs). Our previous study demonstrated a role for TLR9 in the mechanism of experimental autoimmune neuritis (EAN). In this study, we explored whether suppressive oligodeoxynucleotides (sODN) could induce tolerogenic pDCs via TLR9 and thus promote the recovery of EAN. Effects of different TLR9 ligands, CpG ODN and sODN on P0 180-199 peptide-stimulated pDCs were measured by detecting the expression of co-stimulatory molecules, indoleamine 2,3-dioxygenase (IDO), secretion of Th1- and Th2-type cytokines and the TLR9 signaling pathway. CpG ODN- or sODN-treated pDCs were intravenously injected into the EAN mice and their effects were compared. Our data showed that P0180-199 peptides significantly promoted mRNA expression of co-stimulatory molecules (CD40, CD80 and CD86) in pDCs and induced secretion of Th1-type cytokines. Treatment of CpG ODN aggravated the effects of P0 180-199 peptides on pDCs; however, sODN had the opposite effects and significantly upregulated the IDO expression in pDCs. Further analysis showed that MYD88 is necessary for sODN to modulate the TLR9/NF-κB signaling in pDCs. Finally, the sODN-treated pDCs significantly promoted recovery of the EAN mice. Taken together, sODN could induce tolerogenic pDCs and thus ameliorate the EAN.
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China; Central Laboratory, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China.
authors.forename: Yu-Zhong
authors.initials: YZ
authors.lastname: Wang
authors.affiliation: Graduate School of Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China.
authors.forename: Yan-Lei
authors.initials: YL
authors.lastname: Hao
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China.
authors.forename: Hai-Qing
authors.initials: HQ
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China.
authors.forename: Gao-Mei
authors.initials: GM
authors.lastname: Cai
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Surgical Operating Room, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China.
authors.forename: Chun-Xiang
authors.initials: CX
authors.lastname: Jia
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China. Electronic address: jyfyfxg@163.com.
authors.forename: Xun-Gang
authors.initials: XG
authors.lastname: Feng
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China. Electronic address: kqx1970@aliyun.com.
authors.forename: Qing-Xia
authors.initials: QX
authors.lastname: Kong
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics; D051940:B7-2 Antigen / Q000235:genetics; D019013:CD40 Antigens / Q000235:genetics; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C408982:CPG-oligonucleotide; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D012333:RNA, Messenger; C498144:Rela protein, mouse; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D051996:Transcription Factor RelA
keywords: Experimental autoimmune neuritis; Immune tolerance; Plasmacytoid dendritic cells; Suppressive oligodeoxynucleotides