Enhanced susceptibility to low-dose collagen-induced arthritis in CR1/2-deficient female mice--possible role of estrogen on CR1 expression

• Published in: The FASEB journal Vol. 23; no. 8; pp. 2450 - 2458
• Main Authors: Nilsson, Kajsa E, Andrén, Maria, de Ståhl, Teresita Diaz, Kleinau, Sandra
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01-08-2009; Federation of American Societies for Experimental Biology
• Subjects: Adult; Aged; Animals; Arthritis, Experimental - etiology; Arthritis, Experimental - immunology; Arthritis, Experimental - physiopathology; Arthritis, Rheumatoid - etiology; autoimmunity; B cells; B-Lymphocytes - immunology; Base Sequence; complement receptor; DNA Primers - genetics; Estrogens - physiology; Female; Gene Expression; Humans; In Vitro Techniques; knockout mice; Male; MEDICIN; MEDICINE; Mice; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Knockout; Middle Aged; Ovariectomy; Receptors, Complement 3b - deficiency; Receptors, Complement 3b - genetics; Receptors, Complement 3d - deficiency; Receptors, Complement 3d - genetics; Sex Characteristics
• ISSN: 0892-6638; 1530-6860; 1530-6860
• DOI: 10.1096/fj.08-125849

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.--Nilsson, K. E., Andrén, M., Diaz de Ståhl, T., Kleinau, S. Enhanced susceptibility to low-dose collagen-induced arthritis in CR1/2-deficient female mice--possible role of estrogen on CR1 expression.