title: Suppressive oligodeoxynucleotides promote the development of Th17 cells.
abstract: Synthetic oligonucleotides containing repetitive TTAGGG motifs mimic the immunosuppressive activity of telomeric DNA. These suppressive oligonucleotides (Sup ODN) are effective in the treatment/prevention of various inflammatory and autoimmune diseases in mice. The therapeutic activity of Sup ODN was originally attributed to the inhibition of Th1 cell activation. Current results indicate that Sup ODN also promote the maturation of naive CD4(+) T cells into Th17 effectors. The generation of Th17 cells is linked to the prolonged activation of signal transducer and activator of transcription (STAT)3 mediated by suppressor of cytokine signaling 3 (SOCS3) inhibition. In vivo studies show that treatment with Sup ODN promotes Th17 responsiveness under physiological conditions, increasing host resistance to Candida albicans infection. These findings support the development of Sup ODN to suppress pathological inflammatory conditions and improve host resistance to fungal pathogens.
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland, United States of America.
authors.forename: Christian
authors.initials: C
authors.lastname: Bode
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Yang
authors.forename: Hiu
authors.initials: H
authors.lastname: Kiu
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
mesh_terms: D000818:Animals; D001483:Base Sequence; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D002177:Candidiasis / Q000382:microbiology / Q000517:prevention & control; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D054884:Host-Pathogen Interactions / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D009838:Oligodeoxyribonucleotides; C539901:Rorc protein, mouse; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma