J Immunol. 2026 Aug 4;215(8):vkag207. doi: 10.1093/jimmun/vkag207.
ABSTRACT
Sex differences exist in the immune responses to infections and in the prevalence and severity of autoimmune and allergic diseases. These sex differences may be caused by sex hormones and/or variable inactivation of X chromosome genes. The 4 core genotypes mice allow for distinction between the effects of sex hormones and chromosomes on physiology and disease pathology. In the FCG mouse model, the Sry gene is deleted from the Y chromosome and inserted into chromosome 3 as multiple copies of a transgene, allowing for phenotypic male and female mice with XX and XY chromosomes. We sought to investigate the role of sex hormones and chromosomes in respiratory syncytial virus infection and allergen-induced airway inflammation. However, in performing these studies, we found that the immune response in FCG males (XXM and XYM) was significantly blunted. XXF and XYF had 4-fold more CD3+CD4+ T cells and over 7-fold more CD3+CD8+ T cells compared to XXM and XYM in the lungs following stimulus. CD4+ and CD8+ T cells were also significantly decreased in XXM and XYM mice in the lungs, spleen, and peripheral blood at baseline with no effect on B cells, NK cells, or myeloid cells. Thymic T cell numbers were similar among groups, and bone marrow progenitors were unchanged between groups. Overall, the translocation of Sry to chromosome 3 resulted in dramatically decreased immune responses to RSV infection and allergen-challenge, indicating that FCG male mice do not mount appropriate immune responses to a respiratory virus infection.
PMID:42595443 | DOI:10.1093/jimmun/vkag207