Dissecting the Sex and Age Effects in the Immune System Transcriptome

The immune system of an individual is affected by many factors, including sex and age. Males suffer from more frequent and severe infectious diseases compared to females. On the other hand, there are higher rates of autoimmune disease in females. Aging results in higher susceptibility to infectious diseases, weaker response to vaccines, development of autoimmune disorders, and slower healing. However, the molecular changes in the immune system between sexes and with aging are only partially understood.

We characterize sex and age related differences in the immune system using RNA-sequencing of 11 immune cell types from young, adult and old mice of both sexes. Data is from the ImmGen consortium (www.immgen.org).

Hundreds of genes are up-regulated with age - across all immune cell types, lineage specific or cell type specific. As the transcriptional signature of aging includes mostly upregulated genes, it may hint at a loss of repression with age, and does not seem to originate from hematopoietic stem cells. In contrast, only few autosomal genes are differentially expressed between male and female immune cells, and only in macrophages. Those genes are related to innate immunity, potentially indicating that the stronger immune response of females may be due to more activated innate immune pathways prior to pathogen invasion.

Whereas aging affects the expression levels of many genes across all immune cell types, mostly by up regulation, sex only affects few autosomal genes in macrophages. The phenotypic difference between sexes is probably more affected by the different cell frequencies and hormonal stimulation.