Sexual dimorphism in immune response genes as a function of puberty

After the onset of puberty, female mice showed a higher expression of adaptive immune response genes, while males had a higher expression of innate immune genes. This result suggested a requirement for sex hormones. Using in vivo and in vitro assays in normal and mutant mouse strains, we found that reverse signaling through FasL was directly influenced by estrogen, with downstream consequences of increased CD8+ T cell-derived B cell help (via cytokines) and enhanced immunoglobulin production.These results demonstrate that sexual dimorphism in innate and adaptive immune genes is dependent on puberty. This study also revealed that estrogen influences immunoglobulin levels in post-pubertal female mice via the Fas-FasL pathway.The incidence and severity of human diseases vary between the sexes: For example, autoimmune diseases are generally more common in females than in males and are most marked in women of childbearing age [1-3]. Thus, it appears that susceptibility to autoimmunity is expressed at the time of puberty. Puberty is a period of intense molecular, physiological and anatomical reorganization in the body, and the hormonal changes occurring at the time of puberty lay the framework for biological differences that persist throughout life and may contribute to the variable onset and progression of disease in males and females [4]. Sex-related differences in disease susceptibility have also been observed in several mouse models of infectious and autoimmune diseases and may be related to differences in the expression patterns of immune response genes [5,6].Immune responses are sexually dimorphic, both in type and magnitude. Two general systems of immunity to infectious agents have been selected during evolution: innate (natural) immunity, and acquired (adaptive or specific) immunity. The innate immune system uses proteins encoded in the germline (on macrophages, mast cells, natural killer cells) to recognize conserved products of infectious non-self (i.e., microbi