Increased resistance to collagen-induced arthritis in CD44-deficient DBA/1 mice.
OBJECTIVE
To study the role of CD44, the principal hyaluronan (HA) receptor, in experimental arthritis.


METHODS
We generated CD44 gene deficiency in arthritis-susceptible DBA/1LacJ mice to study the role of CD44 directly in collagen-induced arthritis (CIA). 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. The immune status of immunized mice was determined at the end of the experiments. Cell transfer experiments were performed to monitor lymphocyte traffic to the inflamed joints.


RESULTS
Mice homozygous for the CD44 mutation developed normally and showed no phenotypic defects. Although they showed a normal response to immunization 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 serum levels of HA, reduced expression of L-selectin, and a delayed entry of intravenously injected CD44-deficient donor lymphocytes into the arthritic joints of recipient mice.


CONCLUSIONS
While CD44 is not essential for morphogenesis and autoimmunity, this cell surface receptor seems to play an important role in the development of arthritis, most likely by directing leukocyte traffic to the site of inflammation.
Stoop
R
R
Rush Medical College at Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
Kotani
H
H
McNeish
J D
JD
Otterness
I G
IG
Mikecz
K
K
D000818:Animals; D001169:Arthritis, Experimental / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics; D002450:Cell Communication / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D024043:Collagen Type II; D018960:Hyaluronan Receptors / Q000235:genetics*; D006820:Hyaluronic Acid / Q000097:blood; D007113:Immunity, Innate; D007114:Immunization; D015994:Incidence; D007596:Joints / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology
D015815:Cell Adhesion Molecules; D024043:Collagen Type II; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid