In a study published 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.

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The studies were conducted by a team of collaborators including Pedro A. Jose, M.D., Ph.D., at Georgetown University School of Medicine (Washington D.C.), Hironobu Sanada, M.D., Ph.D., Fukushima Medical University (Fukushima, Japan), and Scott Williams, Ph.D., Vanderbilt University (Nashville, TN). Funding for these studies was provided in part by a $10.2 million grant from the National Heart, Lung and Blood Institute.

The grant will allow this group of collaborating investigators, including Dr. Robert M. Carey, M.D. (University of Virginia) to extend their studies on the genetic bases for high blood pressure and salt sensitivity and their mechanisms in subjects from many different ethnic backgrounds, which could influence the predictive value of the diagnostic test. The team's work will examine the normal mechanisms associated with sodium (salt) management by the kidney and how the failure of these mechanisms contributes to high blood pressure.

Dr. Carey will recruit an additional 3,000 volunteers who will receive genetic screens to identify gene variants that contribute to elevated blood pressure. Dr. Jose's research will determine how dopamine receptors and angiotensin II receptors regulate each other. The information from these studies will provide new insights into how hypertension develops, how it can be tested and how it can be treated.

Right now, no definitive diagnostic test exists for salt sensitivity, except for a protocol in which diet is controlled rigorously over a two-week period. "Through these grant funds, we wish to stimulate broader research in the area of cardiovascular disease, hypertension and salt sensitivity," said Dr. Felder. "It's important because cardiovascular diseases, including stroke, account for more disability and death than the next top five causes combined."

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