Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of the p28 subunit of IL-27.
IL-27 is a recently defined family member of the long-chain four-helix bundle cytokines, which consists of EBI3, an IL-12p40-related protein, and p28, an IL-12p35-related polypeptide. The role of IL-27 in the regulation of inflammatory autoimmune diseases has never been studied. The current study uses the DNA vaccination technology, and highly specific Abs to the p28 subunit of IL-27 that were generated by this technology, to delineate its role in the regulation of adjuvant-induced arthritis in Lewis rats. Neutralizing the in vivo function of IL-27 by targeted DNA vaccines and by Abs against IL-27 p28 that were produced in protected donors could rapidly suppress an ongoing disease. Disease suppression was associated with a reduced ex vivo production of inflammatory cytokines. We then used these Abs to investigate the mechanistic basis of disease suppression, showing that IL-27 is not only involved in directing the polarization of naive T cells, but also affects the proliferative response and cytokine production of Ag-specific effector/memory Th1 cells. This may explain, in part, its important role in the regulation of inflammatory autoimmune diseases, and also suggest novel ways of therapy.
Goldberg
Ruth
R
Department of Immunology, Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Wildbaum
Gizi
G
Zohar
Yaniv
Y
Maor
Gila
G
Karin
Nathan
N
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D016207:Cytokines / Q000187:drug effects; D005260:Female; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D010957:Plasmids; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D001323:Autoantibodies; D016207:Cytokines; D007378:Interleukins; D019444:Vaccines, DNA