Sexual differences in immune response appear at puberty

The differences in the male and female immune responses, which make females more prone to autoimmune disease and males more subject to infections, are established during puberty. In a study published today in the open access journal BMC Immunology, researchers identified one of the mechanisms responsible for the difference in immune response between male and female mice. They show that this sexual disparity is established during puberty and is influenced by sex hormones. These findings have implications for studies of autoimmunity, transplantation and vaccination.

Kanneboyina Nagaraju and Eric Hoffman’s groups from the Children’s National Medical Center, Washington DC, USA, and colleagues from other institutions in the USA, used microarrays to study 12,000 genes expressed in the spleen of pre-pubertal, pubertal and post-pubertal male and female mice.

Lamason et al.’s results show that a number of genes are upregulated in both males and females during puberty. The authors found that genes involved in the innate immune response, which provides an immediate defence against pathogens and involves phagocytic cells such as macrophages, were significantly underexpressed in pubertal and post-pubertal females. Genes involved in the adaptive immune response, which provides a long-lasting protection and involves antibodies or ’immunoglobulins’, were overexpressed in pubertal and post-pubertal females compared with males. This difference in expression was not found in pre-pubertal mice, indicating that the sexual disparity in immune system expression is established during puberty. Lamason et al. go on to show that the differences in immunoglobulin expression between males and females are controlled by a gene signalling pathway called the Fas/FasL pathway, which is modulated by the female sex hormone estrogen.