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PMID: 17646407 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Inflammatory arthritis can be reined in by CpG-induced DC-NK cell cross talk.

The Journal of experimental medicine ·Vol. 204 ·No. 8 ·2007-08-06 ·Pages 1911-22

Wu HJ, Sawaya H, Binstadt B, Brickelmaier M, Blasius A, Gorelik L, Mahmood U, Weissleder R, Carulli J, Benoist C, Mathis D

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.

MeSH Terms
Animals Anti-Inflammatory Agents/pharmacology Arthritis/therapy CpG Islands Dendritic Cells/cytology,immunology Immunotherapy/methods Inflammation/therapy Interferon-gamma/metabolism Interleukin-12/metabolism Killer Cells, Natural/cytology,immunology Mice Models, Biological Neutrophils/metabolism Oligonucleotides/chemistry Signal Transduction
Chemicals
Anti-Inflammatory Agents Oligonucleotides Interleukin-12 Interferon-gamma
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Wu Hsin-Jung
Section on Immunology and Immunogenetics, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02115, USA.
Sawaya Heloisa
Binstadt Bryce
Brickelmaier Margot
Blasius Amanda
Gorelik Leonid
Mahmood Umar
Weissleder Ralph
Carulli John
Benoist Christophe
Mathis Diane
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20070285
Published
2007-08-06
Epub
2007-00-23
Pages
1911-22
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118664
Subset
IM
Grants
NIAID NIH HHS · P01 AI054904 · United States
NCI NIH HHS · R24 CA092782 · United States
NIAID NIH HHS · P01 AI54904 · United States
NCI NIH HHS · R24 CA 92782 · United States
External Links
PubMed source DOI: 10.1084/jem.20070285 PMC Full Text View journal details
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