Evaluating the role of candidate gene, csf3r, for sex-linked susceptibility to lupus-like disease in mice

Abstract

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disorder that primarily affects women and this trend is also observed in BWF1 lupus-prone mice. Although the factors that contribute to sex-specific lupus incidence are complex, evidence suggests that sex hormone regulation of genetic targets likely play a role. Several candidate genes have been identified by their disproportionate expression within splenocytes isolated from male and female BWF1 mice and because their expression is regulated by the sex hormone, testosterone. One candidate gene in particular, csf3-r, is predominantly expressed in CD11b+ cells and is the focus of our current studies. Previous research has indicated that Gr1low CD11b+ cells accumulate in male lupus-prone mice, and are associated with disease suppression. We hypothesize that sex-specific expression of csf3-r contributes to the different frequencies of specific neutrophil subpopulations in BWF1 lupus prone mice and may contribute to disease protection in male mice. To test this hypothesis, we are examining the expression levels of csf3r in neutrophils in lupus-prone and nonautoimmune-prone male and female mice and assessing potential correlations between sex-specific expression of csf3r and the frequencies of particular neutrophil subpopulations. The elucidation of testosterone-regulated pathways that contribute to lupus-like disease may point to new therapies that may be beneficial in autoimmune diseases with sex-specific incidences.