Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice

David, A., Trigunaite, A., Macleod, M. K. , Johnson, A. C., Marrack, P. and Jørgensen, T. N. (2014) Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice. Genes and Immunity, 15(3), pp. 153-161. (doi: 10.1038/gene.2014.2) (PMID:24477163) (PMCID:PMC3999239)

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Abstract

Most systemic autoimmune diseases occur more frequently in females than in males. This is particularly evident in Sjögren’s Syndrome, Systemic Lupus Erythromatosis (SLE) and thyroid autoimmunity, where the ratio of females to males ranges from 20:1 to 8:1. Our understanding of the etiology of SLE implies important roles for genetics, environmental factors and sex hormones, but the relative significance of each remains unknown. Using the New Zealand hybrid mouse model system of SLE we present here a new fetal liver chimera-based system in which we can segregate effects of immune system genes from that of sex hormones in vivo. We show that female hematopoietic cells express an intrinsic capacity to drive lupus-like disease in both male and female recipient mice, suggesting that this capacity is hormone independent. Particularly, only chimeric mice with a female hematopoietic system showed significantly increased numbers of germinal center B cells, memory B cells and plasma cells followed by a spontaneous loss of tolerance to nuclear components and hence elevated serum anti-nuclear autoantibodies. A protective effect of testosterone was noted with regards to disease onset, not disease incidence. Thus, genetic factors encoded within the female hematopoietic system can effectively drive lupus-like disease even in male recipients.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macleod, Dr Megan
Authors: David, A., Trigunaite, A., Macleod, M. K., Johnson, A. C., Marrack, P., and Jørgensen, T. N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Genes and Immunity
ISSN:1466-4879

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