title: Inflammatory arthritis can be reined in by CpG-induced DC-NK cell cross talk.
abstract: Unmethylated CpG-oligodeoxynucleotides (ODNs) are generally thought of as potent adjuvants with considerable therapeutic potential to enhance immune responses against microbes and tumors. Surprisingly, certain so-called stimulatory CpG-ODNs strongly inhibited the effector phase of inflammatory arthritis in the K/BxN serum transfer system, either preventively or therapeutically. Also unexpected was that the inhibitory influence did not depend on the adaptive immune system cells mobilized in an immunostimulatory context. Instead, they relied on cells of the innate immune system, specifically on cross talk between CD8 alpha(+) dendritic cells and natural killer cells, resulting in suppression of neutrophil recruitment to the joint, orchestrated through interleukin-12 and interferon-gamma. These findings highlight potential applications of CpG-ODNs and downstream molecules as antiinflammatory agents.
authors.affiliation: Section on Immunology and Immunogenetics, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Wu
authors.forename: Heloisa
authors.initials: H
authors.lastname: Sawaya
authors.forename: Bryce
authors.initials: B
authors.lastname: Binstadt
authors.forename: Margot
authors.initials: M
authors.lastname: Brickelmaier
authors.forename: Amanda
authors.initials: A
authors.lastname: Blasius
authors.forename: Leonid
authors.initials: L
authors.lastname: Gorelik
authors.forename: Umar
authors.initials: U
authors.lastname: Mahmood
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: John
authors.initials: J
authors.lastname: Carulli
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001168:Arthritis / Q000628:therapy*; D018899:CpG Islands; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000628:therapy*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D009841:Oligonucleotides; D018664:Interleukin-12; D007371:Interferon-gamma