Inflammatory arthritis can be reined in by CpG-induced DC-NK cell cross talk.
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.
Wu
Hsin-Jung
HJ
Section on Immunology and Immunogenetics, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02115, USA.
Sawaya
Heloisa
H
Binstadt
Bryce
B
Brickelmaier
Margot
M
Blasius
Amanda
A
Gorelik
Leonid
L
Mahmood
Umar
U
Weissleder
Ralph
R
Carulli
John
J
Benoist
Christophe
C
Mathis
Diane
D
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
D000893:Anti-Inflammatory Agents; D009841:Oligonucleotides; D018664:Interleukin-12; D007371:Interferon-gamma