Verhandelingen van de Koninklijke Academie voor Geneeskunde van België vol:67 issue:2 pages:125-37
Collagen-induced arthritis (CIA) is an animal model for human rheumatoid arthritis. CIA is induced in the mouse by immunization with collagen type II in complete Freund's adjuvant (CFA). As a result of this immunization, mice will develop an autoimmune disease that is characterized by an inflammatory and destructive affection of the joints. IFN-gammaR KO mice have an increased susceptibility to CIA as compared to wild-type control animals: they developed arthritis with a significant earlier disease onset and a higher disease incidence and score. The results indicate that IFN-gamma acts as a disease-protective factor in CIA. The disease-protective effect of IFN-gamma in CIA appeared to be due to CFA that was used for the induction of CIA, and more precisely to the presence of killed mycobacteria in this adjuvant. The killed mycobacteria in CFA elicited in mice an extramedullar myelopoiesis and an expansion of Mac-1+ cells that was strongly inhibited by endogenous IFN-gamma. Parts of the expanded Mac-1+ splenocytes were precursor cells for osteoclasts, they migrated to the joints after challenge with SDF-1, where they found to differentiate into mature osteoclasts who are responsible for bone destruction. The mechanism of expansion, migration and osteoclast activation occurred in IFN-gammaR KO as well as in wild-type mice, but was much more pronounced in the mutant mice. Thus, the use of IFN-gammaR KO mice has exposed a new mechanism in the pathogenesis of autoimmune arthritis in mice. These findings may have important clinical perspectives.