Increased resistance to collagen-induced arthritis in CD44-deficient DBA/1mice

Objective. To study the role of CD44, the principal hyaluronan (HA) recepto r, in experimental arthritis. Methods. We generated CD44 gene deficiency in arthritis-susceptible DBA/1La cJ mice to study the role of CD44 directly in collagen-induced arthritis (C IA). Wild-type and CD44-deficient mice were immunized with chicken type II collagen, and the onset and severity of CIA were monitored up to day 64. Th e immune status of immunized mice was determined at the end of the experime nts. Cell transfer experiments were performed to monitor lymphocyte traffic to the inflamed joints. Results. Mice homozygous for the CD44 mutation developed normally and showe d no phenotypic defects. Although they showed a normal response to immuniza tion with type II collagen and had Th1/Th2 ratios comparable with those in wild-type animals, CD44-deficient mice exhibited significant reductions in both the incidence and severity of CIA. This was accompanied by altered ser um levels of RA, reduced expression of L-selectin, and a delayed entry of i ntravenously injected CD44-deficient donor lymphocytes into the arthritic j oints of recipient mice. Conclusion. While CD44 is not essential for morphogenesis and autoimmunity, this cell surface receptor seems to play an important role in the developm ent of arthritis, most likely by directing leukocyte traffic to the site of inflammation.