S effects on the proportion of splenic CD4+ T cells expressing
S effects around the proportion of splenic CD4+ T cells expressing TFH markers. Effects of PR deficiency on splenic expression of IFN- and ER- gene mRNA levels and activation of antigen presenting cells in aged Nba2 mice We also examined the effects of PR loss around the activation of splenic antigen presenting cells (APCs) as determined by expression on the co-stimulatory molecule, CD86. Generally, CD86 expression on APCs was unaffected by PR loss, except in the case of macrophages (Fig. 8A), where in male mice it was decreased. The opposite impact (not statistically significant) was observed in female mice. We next investigated possible molecular mechanisms linking altered IgG2c autoAb production to loss of PR, a ligand-activated transcription element. We had previously observed that splenic CD4+ T cells from non-autoimmune adult female PR-/- mice over-express IFN gene (ifng) mRNA and protein in vitro, in spite of normal expression of your T-bet gene (tbx21), a transcriptional regulator of IFN- expression and TH1 differentiation (28). Unexpectedly, PR deficiency resulted in drastically decreased ifng expression in total splenic leukocytes from female mice (Fig. 8B); in male mice there was tiny effect. Decreased ifng expression in female PR-/- mice may relate to decreased (T-bet+) TH1 cell abundance (Fig. 6H). In uterine tissue, PR can repress the expression of the ER- gene (esr1); and in female NZB/W mice, esr1 gene deficiency causes selective reduction in serum autoAbs in the IgG2a subclass (equivalent to IgG2c subclass in B6 strains) (15). Nevertheless, PR loss resulted in decreased esr1 mRNA levels in splenic leukocytes from female mice (Fig. 8B), suggesting that PR doesn’t repress IgG2c autoAb production by means of effects on esr1 expression. Interestingly, PR loss had the opposite impact on splenic esr1 expression in male mice. Consequently, sexdependent differences in splenic esr1 expression amongst PR+/+ mice were reversed immediately after PR loss.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptDiscussion and ConclusionsHere we present evidence indicating that PR, a nuclear receptor vital to female reproduction, is involved in regulating splenic CD4+ T cell populations and IgG autoAb production in aged lupus-prone Nba2 mice of both sexes. By comparing female and maleAutoimmunity. Author manuscript; accessible in PMC 2016 April ten.Wong et al.Pagemice, we also recognize an unsuspected function for PR in generating and/or maintaining sexual dimorphism in abundance of splenic leukocyte subsets. In many aged female mice, PR deficiency was associated with markedly increased levels of class-switched IgG2c autoAbs. Though some female PR-/- mice also BMP-2 Protein Molecular Weight showed abnormally higher levels of class-switched IgG1 autoAbs, this phenotype appeared to become much less penetrant than the IgG2c phenotype. IgM autoAbs were the least impacted. Collectively, these results suggest an effect on pathways leading to IgG CSR in autoreactive B cells. We did not observe major effects on B cell abundance or activation, however it is achievable that there were B2M/Beta-2-microglobulin Protein Species important effects on the GC B cell subset, particularly its expression of activation-induced deaminase, which is needed in B cells for CSR and could possibly be under the transcriptional control of PR (15, 41). Constant with this thought, PR loss resulted in lower levels of total IgM in aged female mice (Fig. 1C), suggesting deregulation of CSR may possibly have already been more generalized. The reasonably strong impact on IgG2c autoAbs remains unexplained, but lik.