The Journal of Experimental Medicine
AbD Serotec: Antibody Detectives
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Published online July 23, 2007
doi:10.1084/jem.20070285
The Journal of Experimental Medicine, Vol. 204, No. 8, 1911-1922
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Wu et al.
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ARTICLE

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

Hsin-Jung Wu1, Heloisa Sawaya5, Bryce Binstadt1,2, Margot Brickelmaier4, Amanda Blasius6, Leonid Gorelik4, Umar Mahmood5, Ralph Weissleder5, John Carulli4, Christophe Benoist1,3, and Diane Mathis1,3

1 Section on Immunology and Immunogenetics, Joslin Diabetes Center, 2 Rheumatology Program, Children's Hospital Boston, 3 Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
4 Biogen Idec, Inc., Cambridge, MA 02142
5 Center for Molecular Imaging Research, Massachusetts General Hospital, Charlestown, MA 02114
6 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63101

CORRESPONDENCE Christophe Benoist OR Diane Mathis: cbdm{at}joslin.harvard.edu

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.

Abbreviations used: Ab, antibody; AP, alkaline phosphatase; CAE, chloroacetate esterase substrate; DT, diphtheria toxin; DTR, DT receptor; GPI, glucose-6-phosphate-isomerase; HE, hematoxylin and eosin; HEK, human embryonic kidney; IC, immune complex; IDO, indoleamine 2,3-dioxygenase; IKDC, interferon-producing killer dendritic cell; OD, optimal density; ODN, oligodeoxynucleotide; PAM, pathogen-associated molecule; pDC, plasmacytoid DC; PGN, peptidoglycan; RA, rheumatoid arthritis; TLR, Toll-like receptor.


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