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

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

Nilsson, Kajsa E. (author): Uppsala universitet,Institutionen för cell- och molekylärbiologi

Andrén, Maria (author): Uppsala universitet,Institutionen för cell- och molekylärbiologi

Diaz de Ståhl, Teresita (author): Uppsala universitet,Institutionen för genetik och patologi

Kleinau, Sandra (author): Uppsala universitet,Institutionen för cell- och molekylärbiologi

(creator_code:org_t)

2009-04-07
2009
English.
In: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 23:8, s. 2450-2458

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Nilsson, Kajsa E ...; Andrén, Maria; Diaz de Ståhl, T ...; Kleinau, Sandra

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