Enhanced susceptibility to low-dose collagen-induced arthritis in CR1/2-deficient female mice--possible role of estrogen on CR1 expression.
The influence of complement receptor 1 and 2 (CR1/2) was investigated on the susceptibility to low-dose collagen-induced arthritis (CIA) in wild-type (WT) and CR1/2-deficient DBA/1 mice. Significantly enhanced CIA was observed in female CR1/2-deficient mice compared with WT female mice, while male mutant and WT mice showed similar arthritis development. The enhanced CIA was accompanied with higher complement levels and a prolonged IgM anti-collagen type II response. When investigating whether estrogen contributed to the different arthritis susceptibility, we found that ovariectomy rendered WT females more sensitive to low-dose CIA and to the same extent as CR1/2-deficient females, while CR1/2-deficient mice were unaffected by ovariectomy. Notably, the ovariectomized WT mice displayed reduced CR1(+) B220(+) B-cell numbers and CR1 expression compared with sham-operated WT mice, suggesting a stimulatory effect of estrogen on CR1. In accordance, a significant correlation was observed between reduced CR1 expression in B cells and increased age in healthy female blood donors but not in male donors. Our findings demonstrate an important role of CR1/2 in suppressing CIA in female mice under low-antigen conditions. The data suggest that estrogen promote CR1 expression in B cells. These findings provide insight to the increased frequency of rheumatoid arthritis in postmenopausal women.
Department of Cell and Molecular Biology, Uppsala University, SE-75 124 Uppsala, Sweden.
Kajsa E
KE
Nilsson
Maria
M
Andrén
Teresita
T
Diaz de Ståhl
Sandra
S
Kleinau
D000328:Adult; D000368:Aged; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000209:etiology; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004967:Estrogens / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008875:Middle Aged; D010052:Ovariectomy; D017463:Receptors, Complement 3b / Q000172:deficiency* / Q000235:genetics; D017464:Receptors, Complement 3d / Q000172:deficiency* / Q000235:genetics; D012727:Sex Characteristics
D017931:DNA Primers; D004967:Estrogens; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d