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Enhanced susceptibility to low‐dose collagen‐induced arthritis in CR1/2‐deficient female mice—possible role of estrogen on CR1 expression
Author(s) -
Nilsson Kajsa E.,
Andrén Maria,
De Ståhl Teresita Diaz,
Kleinau Sandra
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-125849
Subject(s) - medicine , endocrinology , estrogen , rheumatoid arthritis , arthritis , estrogen receptor , ovariectomized rat , chemistry , cancer , breast cancer
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., Andren, M., Diaz de Stahl, T., Kleinau, S. Enhanced susceptibility to low‐dose collagen‐induced arthritis in CR1/2‐deficient female mice—possible role of estrogen on CR1 expression. FASEBJ. 23, 2450–2458 (2009)