Enhanced susceptibility to low-dose collagen-induced arthritis in CR1/2-deficient female mice: possible role of estrogen on CR1 expression
2009 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 23, no 8, 2450-2458 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2009. Vol. 23, no 8, 2450-2458 p.
complement receptor, B cells, knockout mice, autoimmunity
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-107312DOI: 10.1096/fj.08-125849ISI: 000268836700013PubMedID: 19351702OAI: oai:DiVA.org:uu-107312DiVA: diva2:228728