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

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

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.

Andrén, MariaUppsala universitet,Institutionen för cell- och molekylärbiologi (author)
Diaz de Ståhl, TeresitaUppsala universitet,Institutionen för genetik och patologi(Swepub:uu)testahl (author)
Kleinau, SandraUppsala universitet,Institutionen för cell- och molekylärbiologi(Swepub:uu)sandklei (author)
Uppsala universitetInstitutionen för cell- och molekylärbiologi (creator_code:org_t)

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

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